The Prion Chronicles: The Story Of Interferon


These are the continuing chronicles of prion disease, the reason for your own state of unease.

For past research and understanding of just what a prion is, see my previous research here:




I wish to pose a question…

Is it possible that, in our efforts to create synthetic drugs (for profit) in order to artificially mimic or replace the body’s natural health and healing processes, even while suppressing the body’s immune response to those drugs so that they may fool the natural system, we have inadvertently created a permanent state of dis-ease as the average human condition?

Let’s take an obscene example.

Over half a century ago, while researching the efficiency of the vaccine for smallpox, Japanese virologists working for the Institute For Infectious Diseases at University of Tokyo published their findings (1954) that some “viral inhibitory factor” was inhibiting the growth of their purposefully induced viral infection of laboratory research rabbits. In other words, the tiny rabbit bodies were having the natural immune response they should, which interferes with the capability of a foreign zoological pathogen to propagate (grow and reproduce) after injection. But they also discovered through isolation of this unknown and naturally occurring preventative substance that it was not originated from antibodies. The desired immunization process of antibody stimulation through vaccination was being profoundly prevented.

Three years later, at the National Institute for medical Research in London, virologists discovered similar causal effects on the growth if influenza virus in chicken egg membranes. Something was again naturally interfering with the growth of the virus after purposeful (unnatural) injection. In their research paper they coined this viral inhibitory factor as “Interferon“.

At the same time, back at the University of Tokyo, those same Japanese virologists finally discovered the essense of what they originally coined as “Viral Inhibitory Factor (VIF)”,  and both research branches agreed that this anti-viral substance was caused by the same class of factors, and eventually these became officially known in medical science as “Interferon” (multiple types).

Further study revealed that these Interferon proteins reside in different human chromosomes, and a purification process of biologically active beta interferon was finally isolated in 1977. By the early 1980’s interferon protein types were isolated and cloned to show conclusive proof that indeed interferons were responsible for interfering with viral reproduction. Eventually, these interferon isolates were used as a treatment for viral infections.

So what are these naturally interfering produced factors, and why do pharmaceutical corporations hate them so much that they seek to interfere with their pre-programmed interference?

Clinically defined, Interferons (IFNs) are proteins (glycoproteins called cytokines) made and released by healthy host cells (naturally occurring cells in your body) in response to the presence of pathogens such as viruses, bacteria, parasites, or tumor cells. They literally act as communication devices traveling as RNA messengers, allowing cells to communicate with each other like micro text messages, creating a trigger effect to “interfere” with disease and viral replication by turning on the protective defensive structure of the immune system that is responsible for activating immune cells (natural killer cells, macrophages, etc.). Interferons also increase the ability of uninfected host cells in their ability to resist new infection by virus (an invading parasite to the host cell), and communicate the known presence of tumor cells to the immune system, up-regulating antigens to T lymphocytes.

A lymphocyte is one of 3 cells from the vertebrate’s immune system found in the lymphatic system called NK (natural killer) cells, B  cells, or T cells. There are currently identified 10 distinct interferons (IFN’s), 7 of which are found in humans. These are further broken down by classes (types 1, 2, and 3). All of these IFN’s are vital for the body’s defense against disease states and infections as well as prevention of tumor growth.

In layman’s terms, we could say that all of the body’s naturally healthy cells send out cell-phone calls in the form of amino acids (proteins), which float through the body as if upon a wirelessly fluid Ethernet, directly connecting to the body’s receiving phone-line like a 911 emergency call; thus literally summoning the body’s first responders in the form of the immune system to send out little firefighter cells (Natural Killer, B, and T-cell lymphocytes) to stop the spread of the fire caused by viral, bacterial, parasitic, or tumor causing pathogens that are invading the host cells.

Those Pesky Little Interferons

While interferons have been used in some cases as a breakthrough yet totally underutilized treatment for the slowing or halting of certain disease growth in humans, we find a much more sinister reason for such research and identification of interferons in modern medicine and vaccine production. You see, the original discovery of interferons was not an altruistic attempt to isolate and synthesize an amino acid compound that would treat disease. In fact, far from it…

Back in 1956, those Japanese and British virologists were not trying to cure disease. No, they were trying to induce disease within their animal subjects for research purposes and spread it into chicken eggs so as to grow the disease for vaccination and “other” purposes; chicken embryo substrates being the most popular method for disease culture growth. But as they learned through continuous interference from the host subjects, something kept getting in the way of their purposeful disease infection of those hosts – an at the time unknown intracellular function of the body as of yet unknown, later to be named as Interferon.

Please understand… in order to vaccinate against disease, these scientists believed that they had to stop the bodies own natural defense against the very disease these scientists were trying to purposefully infect their test subjects with. Some might call this a paradox… or just insanity. In order for their pseudo-science to supposedly work, those virologists had to figure out a way to cut the cell-phone signaling process (now known as interferon) caused by their purposeful inoculate infection of the hosts. They needed to cause the body to cease in its perfectly natural capacity to fight the very disease they were injecting into it, so as to grow the disease within that host body. This would seem to the average person to be, on the surface and rightly so, a counter-productive effort on their part. But then the average person could never comprehend what was happening behind the scenes, let alone the true purpose of funding such experimental “science” as medicine.

Let’s take the phenomenon known as Auto-Immune Deficiency Syndrome (AIDS) for example…

What are its symptoms?

Rare cancerous tumors, viral-like infection, wasting syndrome, and general immune-supression of the lymphatic system.

Sound familiar? Like maybe the body’s phone-lines are down?

The body works though a system of communication devices in bilogical form. When one part or system of the body needs to communicate with another, it does so through a highly advanced structure of expressive signaling and transduction; the release of various types of cells, proteins, and other substances that trigger each inter-dependent system to respond in kind. It is this body-wide platform of cellular communication that is being attacked and blocked by the introduction of inhibiting factors like infectious prions and other melevolent substances.

The body works just fine until it is stung and thus injected (vaccinated) with foreign proteins, DNA, RNA, and other ingreedients that in no other way would ever be able to insert themselves into the body of man (or rabbit).

The main issue with AIDS patients is the lack of the body’s immune response regarding the production of T Lymphocytes, commonly called T-cells. For some reason, despite the body’s many dis-ease states as symptoms of the AID-syndrome,  the body just isn’t getting the hint to produce the very thing that it needs to fight infection. It seems we have a failure to communicate here… For some reason the emergency 911 cell-phone lines seem to be cut, and the first responders (T-cells) are just not being called into action by the healthy cells that are under attack. Their chemical screams for help are going unheard. It’s as if the immune system labor union went on strike, and these “AIDS” symptoms are the resulting chaos and unrest that ensues throughout the body.

Not ironically, these are the same symptoms of what is known as Gulf War Syndrome, a known vaccine induced disease state thought by many researchers to be caused by vaccine adjuvants like squalene and other ingredients injected into the guinea pig soldiers of our military.

But what could possibly cause such a chain reaction throughout the body’s immune-supressive system?

What could possibly have been introduced within the body to prevent its ability to make a protein phone call, just like in those poor test-rabbits so many decades ago?

What is preventing interferon from interfering with the disease process, defeating its attempts to transmit its signal for help to the imune system?

Enter bioengineering and the novel prion…

So how could this novel disease state be simultaniusly spread
throughout Africa and eventually the first world?


Altering Gene Expression: Just A Little Pinprick


“The genetic code is universal….
The complete word-for-word universality of the genetic dictionary is,
for the taxonomist, too much of a good thing.”

–Evolutionist Richard Dawkins, in his book,
‘The Blind Watchmaker’ (1986, p. 270)


“It is recognized by molecular biologists that the genetic code is universal,
irrespective of how different living things are in their external appearances.”

–Creationist Robert Kautz, in his book,
‘The Origin of Living Things’ (1988, p. 44)


“The construction and metabolism of a cell are thus dependent
upon its internal ‘handwriting’ in the genetic code.
Everything, even life itself, is regulated from a biological viewpoint
by the information contained in this genetic code.
All syntheses are directed by this information.”

–A.E. Wilder-Smith, United Nations scientist (1976, p. 254).


“It may seem a platitude to say that the offspring of buttercups, sparrows and human beings are buttercups, sparrows and human beings… What then keeps them, and indeed living things in general, “on the right lines?” Why are there not pairs of sparrows, for instance, that beget robins, or some other species of bird: why indeed birds at all? Something must be handed on from parent to offspring which ensures conformity, not complete but in a high degree, and prevents such extreme departures. What is it, how does it work, what rules does it obey and why does it apparently allow only limited variation? Genetics is the science that endeavours to answer these questions, and much else besides. It is the study of organic inheritance and variation, if we must use more formal language.”

–British geneticist, E.B. Ford,
‘Understanding Genetics’ (1979, p. 13).


“Tablets of stone prepared by the Babylonians some 6,000 years ago have been interpreted as showing pedigrees of several successive generations of horses, thus suggesting a conscious effort toward improvement. Other stone carvings of the same period illustrate artificial cross-pollination of the date palm as practiced by the early Babylonians. The early Chinese, many years before the Christian era, improved varieties of rice. Maize was cultivated and improved in the western hemisphere by the American Indians, beginning at an early period in their history. In another era, Hippocrates, Aristotle, and other Greek philosophers made observations and speculations suggesting genetic principles.”

–Eldon Gardner, ‘The History of Biology’ (1972, pp. 399-400)


“And God said, let the earth put forth grass, the herb
yielding seed,  and the fruit tree yielding fruit after its kind,
wherein is the seed thereof upon the earth, and it was so.
And the earth brought forth grass, the herb yielding seed and
the fruit tree yielding fruit after its kind whose seed was in itself.”

–The Bible, Genesis 1:11-12


“In the first chapter of Genesis, however, because it is a matter of the greatest religious importance, the Bible speaks clearly and finally on a matter of biology. After its kind is the statement of a biological principle that no human observation has ever known to fail. The most ancient human records engraved on stone or painted on the walls of caves bear witness to the fact that horses have ever been horses, bears have ever been bears, geese have ever been geese, reindeer have ever been reindeer. The most desperate and subtle efforts of man in modern times have been unable to alter this divine decree. The Bible teaches that from the beginning there have been a large number of types of living things, man included, which were so created as to remain true to their particular type throughout all generations…. The latest results of modern biological research, Mendel’s Laws, agree exactly with what was written by Moses three thousand years ago—and they also elucidate it…”

Byron Nelson, ‘After Its Kind’, (1967, pp. 3,103)


“…once a fertilized, (a) single human cell begins to develop, the original plans are
faithfully copied each time the cell divides (a process called mitosis)
so that every one of the thousand million million cells in my body, and in yours,
contains a perfect replica of the original plans for the whole body”.

–Evolutionist John Gribbin (1981, p. 193)


“The Nobel laureate, F.H. Crick has said that if one were to
translate the coded information on one human cell into book form,
one would require one thousand volumes each of five hundred pages to do so.
And yet the mechanism of a cell can copy faithfully at cell division
all this information of one thousand volumes each of
five hundred pages in just twenty minutes.”

–Dr. Wilder-Smith (1976, p. 258).


“Every organism has in it a store of what is called genetic information… I will refer to an organism’s genetic information store as its Library…. Where is the Library in such a multicellular organism? The answer is everywhere. With a few exceptions every cell in a multicellular organism has a complete set of all the books in the Library. As such an organism grows its cells multiply and in the process the complete central Library gets copied again and again…. The human Library has 46 of these cord-like books in it. They are called chromosomes. They are not all of the same size, but an average one has the equivalent of about 20,000 pages…. Man’s Library, for example, consists of a set of construction and service manuals that run to the equivalent of about a million book-pages together.”

“It is an indication of the sheer complexity of E. coli
that its Library runs to a thousand page-equivalent”

–A.G. Cairns-Smith  (1985, pp. 9,10,11)


“The DNA in living cells contains coded information. It is not surprising that so many of the terms used in describing DNA and its functions are language terms. We speak of the genetic code. DNA is transcribed into RNA. RNA is translated into protein. Protein, in a sense, is coded in a foreign language from DNA. RNA could be said to be a dialect of DNA. Such designations are not simply convenient or just anthropomorphisms. They accurately describe the situation.”

–Lester and Bohlin (1984, pp. 85-86)


Further, consider that human beings have learned to store information on
clay tablets, stone, papyrus, paper, film, cassettes, microchips, etc.
Yet ‘human technology has not yet advanced to the point of
storing information chemically as it is in the DNA molecule


“It is not possible for a code, of any kind, to arise by chance or accident.
The laws of chance or probability have been worked out by mathematics…
A code is the work of an intelligent mind. Even the cleverest dog or chimpanzee
could not  work out a code of any kind. It is obvious then that chance cannot do it…
This could no more have been the work of chance or accident than could the
“Moonlight Sonata” be played by mice running up and down the keyboard of my piano!
Codes do not arise from chaos”

–Professor Andrews (1978, pp. 28,29).

Infecting The World
Through Vaccination


So what happens when man comes clumsily and irresponsibly into the age of molecular science, where he begins to intermix species through inoculation? How can man know if his limits truly are what is written in the ancient scriptures and philosophies of moral men unless he seeks the answers by destroying the perfection of nature’s mathematical equations of the biology of life? How can we know the limits of genetically altered life if we don’t push those limits to the very brink of extinction of species, including our own?

Ancient warnings are for pussies!!!

In my previous research, I have postulated the horrifyingly evidence-based theory that all modern disease states, from the dementia’s to cancer to AIDS, have been induced through the vaccination process via the direct bodily injection of foreign “infectious” proteins called prions. Further research has all but confirmed the reality of this notion, showing that the inherent protective foundation of these cellular proteins in cell health (before infection) are essential to life itself.


Prion protein aids bone marrow

New study findings point to possible stem cell role for normal form of protein

By Charles Choi | January 31, 2006

The normal form of prion protein (PrP) appears necessary for bone marrow stem cells to renew themselves, scientists reported online this week in the Proceedings of the National Academy of Sciences. These findings suggest a potential physiological function in stem cells for the normal form of the widely expressed protein. “Prior to this work there was no hint that PrP had a function in stem cell biology,” co-author Andrew Steele at the Whitehead Institute for Biomedical Research in Cambridge, Mass., told The Scientist. “We are now looking into PrP function in other adult stem cells, particularly neural stem cells.” Prions are infamous for being associated with transmissible spongiform encephalopathies (TSEs) such as mad cow disease, but the function of PrP — the normal, widespread and highly conserved form of prions — remains a mystery. In preliminary studies, co-author Cheng Cheng Zhang discovered 40% of adult mouse bone marrow cells expressed PrP on their surfaces. More than 80% of these PrP-marked cells were red blood cells or their developmental precursors, suggesting PrP might be a marker for long-term hematopoietic stem cells, which can give rise to the entire adult blood system. To determine if PrP was a marker for long-term hematopoietic stem cells, the researchers took bone marrow cells from wild-type mice and purified them into fractions, some of which expressed PrP. Six months after transplantation into lethally irradiated mice, the researchers saw both short- and long-term engraftment in mice that received PrP-containing cells, but only short-term engraftment activity in mice receiving non-PrP cells. While PrP is a marker for long-term hematopoietic stem cells in wild-type mice, PrP-knockout mice still possess these cells, as well as relatively normal levels of their derived progeny. To determine what function PrP might normally have in hematopoietic stem cells, the researchers carried out several rounds of bone marrow implantations. First they transplanted bone marrow from either wild-type mice or a PrP-null strain into lethally irradiated mice. When the engrafted marrow flourished and generated peripheral blood cells, the researchers implanted the newly reconstituted bone marrow into another lethally irradiated mouse group, then repeated the process a third time. In each round after the first, bone marrow originating from PrP-null mice experienced a dramatically reduced ability to renew itself, while cells from the wild-type mice did not. Retroviral infections that expressed PrP in recipients of PrP-null bone marrow rescued this defective process, suggesting PrP is necessary for hematopoietic stem cell self-renewal. Odile Kellerman at the Pasteur Institute in Paris, who did not participate in this study, noted prions often trigger neuron death in TSEs after long incubation periods,” similarly, PrP only impacted hematopoietic stem cells over the long term. “In both cases, PrP appears to contribute to the long-lasting adaptation of cells to injury,” she told The Scientist. Kellerman suggested that when PrP function is disrupted, cells try to adapt, “but in the long term, this turns out to be detrimental.” The exact mechanism behind how PrP might contribute to hematopoietic stem cell renewal remains unknown. Co-author Harvey Lodish speculated PrP might bond to and concentrate a hormone on the cell surface, or help stem cells adhere to neighboring cells or extracellular matrix. “It should prove fairly straightforward to see if it is adhering to other proteins or any known or unknown hormones,” he told The Scientist. William Stanford at the University of Toronto, who did not participate in this study, noted that PrP is tethered to cell membranes via a glycosylphosphatidylinositol (GPI) anchor, similar to hematopoietic stem cell marker Sca-1. “This suggests these GPI-anchored proteins, which have similar functions, may operate through a common mechanism,” Stanford told The Scientist. Future experiments could investigate whether overexpressing PrP in hematopoietic stem cells increases self-renewal, and rescues self-renewal defects such as in the Sca-1 deficient mouse, Stanford added — or if genetically substituting PrP with a different GPI-anchored protein rescues the self-renewal defect seen in PrP-null mice. Links within this article C.C. Zhang et al. “Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal.” PNAS Early Edition.
Published online January 30, 2006. B.A. Maher.
“Prion hypothesis proven?” The Scientist, April 21, 2005.
M. Fogarty. “Prions – The terminators.” The Scientist, July 28, 2003.
M. Fogarty. “Researchers further define sources of adult blood stem cells.” The Scientist, September 16, 2002.
J.U. Adams. “The tiniest of life’s rafts.” The Scientist, October 11, 2004


Neurons and Astrocytes Respond to Prion Infection by Inducing Microglia Recruitment


The accumulation and activation of microglial cells at sites of amyloid prion deposits or plaques have been documented extensively. Here, we investigate the in vivo recruitment of microglial cells soon after intraocular injection of scrapie-infected cell homogenate (hgtsc+) using immunohistochemistry on retinal sections. A population of CD11b/CD45-positive microglia was specifically detected within the ganglion and internal plexiform retinal cell layers by 2 d after intravitreal injection of hgtsc+. Whereas no chemotactism properties were ascribed to hgtsc+ alone, a massive migration of microglial cells was observed by incubating primary cultured neurons and astrocytes with hgtsc+ in a time- and concentration-dependent manner. hgtsc+ triggered the recruitment of microglial cells by interacting with both neurons and astrocytes by upregulation of the expression levels of a broad spectrum of neuronal and glial chemokines. We show that, in vitro and in vivo, the microglia migration is at least partly under the control of chemokine receptor-5 (CCR-5) activation, because highly specific CCR-5 antagonist TAK-779 significantly reduced the migration rate of microglia. Activated microglia recruited in the vicinity of prion may, in turn, cause neuronal cell damage by inducing apoptosis. These findings provide insight into the understanding of the cell-cell communication that takes place during the development of prion diseases.



Prion hypothesis proven?

In vitro infectivity study in Cell stirs tempest in a test tube

By Brendan Maher ( | April 21, 2005

Protein aggregates generated in a test tube infected wildtype hamsters with a disease much like scrapie, according to an article appearing this week in Cell. Such a demonstration has, in the past, been called the gold standard of proof for the prion hypothesis, Stanley Prusiner’s Nobel-winning assertion that infectious, self-replicating protein isoforms are the culprit in transmissible spongiform encephalopathies (TSEs) like scrapie, Creutzfeldt-Jakob disease, and mad cow disease.

Study coauthor Claudio Soto, said that this demonstration, together with a paper published by Prusiner’s group last summer, should allay most doubts. “There is really little room for skepticism,” he told The Scientist.

But the study has done little to quiet prion hypothesis skeptics. “I’m not going to abandon alternative hypotheses for the time being,” said Robert A. Somerville of the Institute for Animal Health, Edinburgh.

While Prusiner’s group had successfully infected a mouse with a recombinant protein derived from bacteria, some argued that their use of transgenic mice susceptible to the disease undercut the power of the demonstration. In the new study, researchers at the University of Texas Medical Branch, Galveston, Universidad Autonoma, Madrid, and the University of Chile in Santiago fine-tuned a cyclical process for amplifying aggregated protein from an infected hamster brain. Through serial dilutions, they were able to infect a wildtype hamster with in vitro–produced aggregates without any traces of the original infectious brain. But skeptics, including a member of Prusiner’s group, argue that using material from a diseased hamster brain could have resulted in residual contamination.

Soto’s group has been using a process that they call protein misfolding cyclic amplification (PMCA), which aids the aggregation of the normal cellular protein PrPc into the misfolded, polymer-forming PrPres that is associated with TSE pathology. The process works in a fashion similar to polymerase chain reaction (PCR) amplification of oligonucleotides. After seeding PrPc with PrPres, the solution is incubated and sonicated. “Once the aggregates become long enough, we split them into smaller pieces so that in a new conversion, a new incubation, they are able to convert more and more of the normal protein,” Soto explained.

Crucially, however, the PrPres “seed” comes from infected hamster brain homogenate, while the normal PrPc comes from healthy hamster brain homogenate. “They actually started from infectious material, and we didn’t,” said Giuseppe Legname, of the University of California, San Francisco, and co-author on the Prusiner paper. “It’s an alternative approach to demonstrate that you might make prions, but to say that these are synthetic prions, it’s very difficult.”

Soto insisted that serial dilutions between rounds of PMCA reduce scrapie brain homogenate to an amount equivalent to a 10 to the minus 10th and a 10 to the minus 20th–fold dilution. Infectivity generally drops off after 10 to the minus 9th, according to the paper. “We’ve completely ruled out the possibility that the infectivity is still remaining from… the original brain,” Soto said...



While the article continues to criticize the control group results, which you may read at the link above, the important point here is that scientists are creating prions and making them purposefully more infectious. They are testing them in various substances and frequencies. And through the ultra-sound sonic vibration described above as protein misfolding cyclic amplification (PMCA), they are able to excite the growth factor of infectious prions so that they take over (mis-fold) healthy brain tissue much quicker. This PMCA process is used in autopsy to detect prion disease.

I have my own concerns that these ultra-sound frequencies are the same as used in cell-phone towers and in the process of ultra sound for unborn infants and other medical procedures, as well as other frequencies unknown via smart meters, radio waves, etc. We are playing with the fuel for the fire and there is virtually no escaping this permanent state of sonic bombardment…

It is also interesting to note that two men wsere cured of AIDS symptoms by receiving a bone marrow transfusion not so long ago…

(CBS News) Two men who’ve had HIV for years may now be free of the disease following bone marrow transplants, researchers at Brigham and Women’s Hospital in Boston announced Thursday.

The new research has some attendees at the XIX International AIDS Conference in Washington, D.C. hopeful for a cure.

Timothy Ray Brown, man thought to be first “cured” of AIDS, says he’s still cured
Man “cured” of AIDS: Timothy Ray Brown

Both patients were being treated for cases of cancer. One of the patients underwent a bone marrow transplant two years ago at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, the other had the procedure done four years ago at the same hospital. reports that one of the patients is in his 50s and has been infected since the early 1980s towards the beginning of the AIDS epidemic and the other man, in his 20s, was infected at birth.

Both stayed on their antiretroviral medication regimens, the standard treatment of HIV, following the transplants.

The researchers discovered that overtime as the patients’ cells were replaced by cells from the donor, evidence of HIV in the patients’ blood tests disappeared. The researchers also said both patients have no signs of HIV in their DNA or RNA and levels of their disease-fighting antibodies have also decreased. The researchers think the medications helped allow these cells to be replaced.

“This gives us some important information,” one of the researchers Dr. Daniel Kuritzkes, an infectious disease specialist at the hospital and Harvard Medical school said in a press release. “It suggests that under the cover of antiretroviral therapy, the cells that repopulated the patient’s immune system appear to be protected from becoming re-infected with HIV.”

The researchers themselves won’t call it a cure yet, saying they still need to check more tissues for traces of the disease. But they were surprised to see no signs of HIV beyond what’s seen in a blood test.

We expected HIV to vanish from the patients’ plasma, but it is surprising that we can’t find any traces of HIV in their cells,” said co-resarcher Dr. Timothy Henrich, also of BWH and Harvard. “The next step is to determine if there are any traces of HIV in their tissue.”

The researchers’ announcement comes days after Timothy Ray Brown, the man known as the “Berlin Patient,” held a press conference in Washington, D.C.,  to say he’s still cured of AIDS five years after undergoing a bone marrow blood transplant



It is important to note that the chemokine receptor-5 (CCR-5) antagonist prevents the cellular binding of the HIV-1 virus, as is explained in this video:


And how do these prions effect disease states?

Let’s take for example Multiple Sclerosis:

“The etiology of Multiple Sclerosis (MS) is unknown. Existing epidemiologic data suggests that MS can be an infectious disease. MS used to be classified as one of the ‘slow infections‘–many of these are caused by prions. Prions are small, proteinaceous, infectious particles–distinguished from viruses by the absence of intrinsic nucleic acids. In a contrast to the ‘classic’ prional diseases (Kuru, Scrapie or Creutzfeldt-Jacob Disease) that in CNS affect primarily neurons, the ‘target’ cell in MS is an oligodendrocyte. This may explain differences in disease presentation. This paper presents a pathophysiological model of MS based on the assumption that MS is a prional disease. Processes leading to the demyelination in Multiple Sclerosis seem also to involve lymphocytes, astrocytes and macrophages as well as the interferon system…”



NOTE: The protein that prions are made of (PrP) is found throughout the body, even in healthy people and animals, and necessarily protects cells from infections. However, PrP found in infectious material has a different structure and is resistant to proteases, the enzymes (proteins) in the body that can normally break down other proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc — the C refers to healthy ‘cellular‘ PrP, while the Sc refers to infectious ‘scrapie‘, the prototypic prion disease, occurring in sheep. The infectious isoform of PrP, known as PrPSc, is able to convert normal PrPC proteins in humans into this infectious isoform by changing their conformation, or shape. This, in turn, alters the way the proteins interconnect, creating symptoms like transmissible spongiform encephalopathy (holes in the human brain like mad cow disease). PrPSc always causes prion disease. In the end, no cellphone call can be made if the interferon protein is infected and mis-folded before it is able to reach its receiving protien that would activate T-Cells or other immune responses. Another word for mis-fold might be easier to understand as to misinform. The immune system is being lied to in a strange, chemically unbalanced way due to prion protein infections (mis-folding). Sheep blood (serum) is a popular vaccine substrate to grow vaccines for humans upon, and the protein and DNA cannot be filtered out of the final vaccine product. There are no other viable explanations why infectious prions from animals would intermingle within a human body (xenotransplantaion/xenografting).

A thorough and sourced description about prions can be found here:

This interference that infectious prions cause to interferon and other protein-based signaling and transcription cells is shown in the research studies below. For those with the gumption, let’s play a biological game of connect the dots.



Prion infection is accelerated in (interferon type 3) IRF3-deficient mice…

The IRF3-dependent pathway is protective against prion infection in cell culture.

We tested whether over-expression of IRF3 (interferon) could affect the production of PrPSc (infectious/mis-folded prions) in the cell culture models. The level of PrPC (healthy prions) was not affected by the transient expression of the genes in uninfected N2a58 cells (data not shown). PrPSc was significantly decreased by overexpression of IRF3 in the 22L-N2a58 cells (Fig. 5A). We confirmed that the activated form of IRF3 (phosphorylated at Ser396 of IRF3) increases in a dose-dependent manner after transfection of the IRF3 gene in both 22L-N2a58 cells (Fig. 5A) and uninfected N2a58 cells (data not shown), indicating that the upregulation of IRF3 phosphorylation seen in the Fig. 5A is most likely due to an increase in the level of IRF3 protein after transfection.

To investigate the effect of downregulation of IRF3 in the 22L-N2a58 cells, we performed knockdown experiments using small interfering RNAs (siRNAs). IRF3 expression was significantly decreased by two types of siRNAs against IRF3, whereas β-actin expression, as the internal standard, was not changed (Fig. 5B)… These data suggest that IRF3 has an inhibitory effect on the production of PrPSc in the 22L-N2a58 cells.

To further evaluate the protective effect of IRF3… After incubation with 22L-infected BH (22L-BH), the cell clones were subcultured for five passages and analyzed by Western blotting with anti-PrP antibodies. The values of the PrPSc/PrPC ratio were inversely correlated with the values of the IRF3/beta-actin ratio (Fig. 5C), indicating that enhanced expression of IRF3 effectively blocks new prion infection.


In the present study, we found that a genetic deficiency of IRF3 accelerates the progression of TSE (transmissable prion disease) following i.p. transmission in mice and that the accumulation rate of PrPSc in the spleen is increased in the IRF3−/− mice. Furthermore, we demonstrated that IRF3 has an inhibitory effect on PrPSc accumulation and that the levels of IRF3 are inversely correlated with resistance to prion infection in cell culture.

IRF3 is known to be constitutively expressed in many tissues and cells (6, 22, 45). Indeed, we confirmed the expression of IRF3 in brains (data not shown) and N2a58 cells (Fig. 5). Furthermore, not only glial cells but also neurons express most innate immunity-related genes and produce type I IFN in response to virus infection (11). Although the role of IRF3 in prion propagation into the CNS is still unclear, we speculate that an absence of IRF3 signaling leads to increased prion replication not only in peripheral tissues but also in the CNS. It would be of great value to examine this further using neuron-specific IRF3-disrupted mice or neuron-specific IRF3-expressing mice.

It was reported in prion infection that genetic disturbance of TLR4 (36) or interleukin-10 (IL-10) (41) leads to shorter incubation periods of prion infection. Since these, respectively, are an upstream and a downstream factor of the IRF3-mediated pathway, the findings may be due in part to functional changes in IRF3-mediated signaling.

Based on these results, two hypothetical models are proposed to explain the inhibitory effect of IRF3 on the prion infection. The first is that MyD88-independent pattern recognition receptors (PRRs), such as TLR3, TLR4, or RIG-I/MDA5, might recognize prion, and the resulting activation of IRF3 could induce various IRF3-responsive genes that may participate in the protective effect. The fact that the in vivo administration of IFNs (interferons), a representative of the IRF3-responsive genes, previously failed to show inhibitory effects on TSE (13, 16) suggests that IRF3-responsive genes other than IFNs may be important for the inhibitory effect of IRF3 on prion infection. Of note, the protective effect of IRF3 against several viruses has been suggested to be largely independent of the production of type I IFN and is probably responsible for the antiviral actions of specific IRF3-responsive genes (10, 18, 21). Peritoneal macrophages from wild-type mice moderately induced tumor necrosis factor alpha (TNF-α) or IL-6 following exposure to PrPSc-mimicking PrP peptides (PrP residues 106 to 126 or PrP residues 118 to 135), whereas TLR4 signaling-mutant mice were impaired in their ability to produce these cytokines (36), supporting in part the hypothesis that some PRRs may sense PrPSc as a sort of PAMP. On the other hand, it should be noted that the MyD88-independent pathway activates both NF-κB and IRF3. Although the induction of proinflammatory cytokines essentially depends upon NF-κB, it was unclear whether the activation of IRF3 was induced by these PrP peptides. In fact, the hallmarks of IRF3 activation, such as phosphorylation, dimerization, and cytoplasm-to-nucleus translocation of IRF3 in 22L-N2a58 cells, were not detected (data not shown). Moreover, it was previously reported that IFNs were not detected in the serum, spleens, or brains of mice infected with scrapie (44). In addition, IFN-β mRNA does not increase in the brains of CJD (human prion disease) patients (7) or mice infected with ME7 prion strain (14). Hence, these results argue against the notion that the IRF3-mediated signaling is activated by prion infection, but it remains to be determined whether transient and weak responses are evoked at an early phase in the infection. The question as to whether IRF3-mediated signaling directly suppresses the production of PrPSc or increases its degradation also remains open.

Another explanation is that prion infection itself may have little effect on the pathway but that the basal activity of IRF3 may have some degree of inhibitory effect on prion propagation. It has been reported that IRF3 can be activated not only by viruses but also by multiple activators such as cellular stress and DNA damage (24, 34). Accordingly, it is possible that constitutive activation of IRF3, albeit at a low level, occurs in the brain even in the absence of a pathogen. This notion is further supported by the fact that constitutive, weak IFN signaling in the absence of viral infection plays a role in modifying cellular responsiveness in the immune and other biological systems (38, 40). Accumulating evidence indicates that many viruses have evolved to evade the innate immune system, including IRF3-mediated signaling (15, 23). For instance, an active mutant of IRF3 has been reported to exert a markedly suppressive effect on cellular HIV-1 infection, and administration of poly(I·C) potently inhibits HIV-1 replication in microglia through a pathway requiring IRF3. Nonetheless, HIV-1 itself does not activate IRF3 but, rather, decreases IRF3 protein in HIV-1-infected cells (12, 37). Likewise, prion infection might disturb the activation of IRF3 even though prion is considered to be largely composed of PrPSc. We are currently investigating this possibility. Furthermore, an analogy can be made between the role of IRF3 in prion infection and that of IL-10. The levels of IL-10 are not increased in the brains of scrapie-infected mice (14, 42), whereas IL-10 knockout mice are highly susceptible to the development of scrapie (41).

In conclusion, we have shown that IRF3, a key transcription factor of the MyD88-independent pathways, operates in the host defense machinery against prion infection. The findings provide new insight into understanding of the innate immunity to prion infection.



Interleukin-10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, IL-10 is encoded by the IL10 gene.[1]

Gene and protein structure

The IL-10 protein is a homodimer; each of its subunits is 178-amino-acid long.[2]

IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29).[3]

Expression and synthesis

In humans, IL-10 is encoded by the IL10 gene, which is located on chromosome 1 and comprises 5 exons,[1] and is primarily produced by monocytes and, to a lesser extent, lymphocytes, namely type 2 T helper cells (TH2), mastocytes, CD4+CD25+Foxp3+ regulatory T cells, and in a certain subset of activated T cells and B cells.

In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolocules like proteins or nucleic acids. It is a quaternary structure of a protein.

A homo-dimer would be formed by two identical molocules (a process called homodimerization). A hetero-dimer would be formed by two different macromolecules (called heterodimerization).

Most dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer would be the enzyme reverse transcriptase, which is composed of two different amino acid chains.[1] An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO.[2]

Some proteins contain specialized domains to ensure dimerization (dimerization domains).

Examples of Homodimer include anti-bodies and Factor VII.

Microglia are a type of glial cell that are the resident macrophages of the brain and spinal chord, and thus act as the first and main form of active immune defense in the central nervous system (CNS).

Microglia constitute 10-15% of the total glial cell population within the brain.[1] Microglia (and astrocytes) are distributed in large non-overlapping regions throughout the brain and spinal cord.[2][3] Microglia are constantly scavenging the CNS for plaques, damaged neurons and infectious agents.[4] The brain and spinal cord are considered “immune privileged” organs in that they are separated from the rest of the body by a series of endothelial cells known as the blood-brain barrier, which prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (few antibodies are small enough to cross the blood brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.[5] They achieve this sensitivity in part by having unique potassium channels that respond to even small changes in extracellular potassium.

Microglial cells differentiate in the bone marrow from hematopoietic stem cells, the progenitors of all blood cells. During hematopoiesis, some of these stem cells differentiate into monocytes and travel from the bone marrow to the brain, where they settle and further differentiate into microglia.[6]

Monocytes can also differentiate into myeloid dendritic cells and macrophages in the peripheral systems. Like macrophages in the rest of the body, microglia use phagocytic and cytotoxic mechanisms to destroy foreign materials. Microglia and macrophagesboth contribute to the immune response by acting as antigen presenting cells, as well as promoting inflammation and homeostatic mechanisms within the body by secreting cytokines and other signaling molecules.

In their downregulated form, microglia lack the MHC class I/MHC class II proteins, IFN-γ cytokines, CD45 antigens, and many other surface receptors required to act in the antigen-presenting, phagocytic, and cytotoxic roles that hallmark normal macrophages. Microglia also differ from macrophages in that they are much more tightly regulated spatially and temporally in order to maintain a precise immune response.[7]

Another difference between microglia and other cells that differentiate from myeloid progenitor cells is the turnover rate. Macrophages and dendritic cells are constantly being used up and replaced by myeloid progenitor cells which differentiate into the needed type. Due to the blood brain barrier, it would be fairly difficult for the body to constantly replace microglia. Therefore, instead of constantly being replaced with myeloid progenitor cells, the microglia maintain their status quo while in their quiescent state, and then, when they are activated, they rapidly proliferate in order to keep their numbers up. Bone chimera studies have shown, however, that in cases of extreme infection the blood-brain barrier will weaken, and microglia will be replaced with haematogenous, cart-marrow derived cells, namely myeloid progenitor cells and macrophages. Once the infection has decreased the disconnect between peripheral and central systems is reestablished and only microglia are present for the recovery and regrowth period.


Transport of prion protein across the blood–brain barrier


The cellular form of the prion protein (PrPc) is necessary for the development of prion diseases and is a highly conserved protein that may play a role in neuroprotection. PrPc is found in both blood and cerebrospinal fluid and is likely produced by both peripheral tissues and the central nervous system (CNS). Exchange of PrPc between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications, but it is unknown whether PrPc can cross the blood–brain barrier (BBB). Here, we found that radioactively labeled PrPc crossed the BBB in both the brain-to-blood and blood-to-brain directions. PrPc was enzymatically stable in blood and in brain, was cleared by liver and kidney, and was sequestered by spleen and the cervical lymph nodes. Circulating PrPc entered all regions of the CNS, but uptake by the lumbar and cervical spinal cord, hypothalamus, thalamus, and striatum was particularly high. These results show that PrPc has bidirectional, saturable transport across the BBB and selectively targets some CNS regions. Such transport may play a role in PrPc function and prion replication.


Cellular prion protein (PrPc) is perhaps best known as a source for the misfolded protein PrPsc (Prusiner, 1997) and as a prerequisite for the development of prion diseases (Mallucci et al., 2000). However, PrPc itself likely has important biological functions. It is found circulating in blood (Volkel et al., 2001) and is found in even higher levels in the cerebrospinal fluid (CSF) (Picard-Hagen et al., 2006). After ischemic events, PrPc levels increase in blood (Mitsios et al., 2007) and in neurons and brain endothelial cells in the peri-infarct region (Mitsios et al., 2007; Weise et al., 2004). These increases may reflect cytoprotective and neuroprotective roles for PrPc as recently reviewed (Roucou & LeBlanc, 2005). PrPc null mice have larger infarct volumes after ischemic events (Weise et al., 2006; Nasu-Nishimura et al., 2008) and more neuronal apoptosis after viral infections (Nasu-Nishimura et al., 2008) than wild type mice. In comparison, mice that overexpress PrPc have smaller infarcts and better neurological outcomes than wild type mice after ischemic events (Shyu et al., 2005). These protective events are likely mediated by PrPc through activation of anti-apoptotic (Spudich et al., 2005) and anti-oxidant pathways (White et al., 1999).

Sources of circulating PrPc likely include platelets (Robertson et al., 2006), endothelial cells (Simak et al., 2002), and lymphocytes (Politopoulou et al., 2000). Among lymphocytes, CD3 and CD8 lymphocytes have especially high levels which increase with aging (Politopoulou et al., 2000). All these cells have membrane bound PrPc that apparently can be released into the circulation. Platelet activation (Robertson et al., 2006) or endothelial apoptosis (Simak et al., 2002), for example, results in release of PrPc from those cells.

Thus, PrPc occurs in both blood and in CSF with levels that are likely responsive to disease states. This raises the question of whether PrPc can cross the blood–brain barrier (BBB). Such passage could link the two pools of PrPc and the events that control their levels. Here, we examined the ability of PrPc to cross the BBB in both the blood-to-brain and the brain-to-blood directions.

Capillary depletion

Capillary depletion as modified for use in the mouse (Triguero et al., 1990; Gutierrez et al., 1993) was used to determine the degree to which PrPc was sequestered and retained by the vascular bed of the brain.

I-PrPc was also taken up by the peripheral tissues of spleen, liver, kidney and cervical lymph nodes (Table 2)… there was a statistically significant decrease in the Ki for brain: F(1,8) = 7.97, p <0.05. This demonstrates that transport of PrPc across the BBB involves a saturable transport system.

Fig. 4 shows values for brain and spinal cord regions. Statistical comparison of the whole brain value to brain regions and olfactory bulb (spinal cord regions excluded) showed a statistically significant variation: F(22,62) = 18.3, p <0.001. The hypothalamus, thalamus, and striatum showed statistically (p <0.01) greater uptake in comparison to whole brain. The highest uptake, however, was into the lumbar region of the spinal cord. Inhibition of uptake by unlabeled PrPc (Table 3; p <0.05) was found for whole brain, olfactory bulb, 4 of the 10 brain regions (occipital cortex, thalamus, striatum, and midbrain) and two of the spinal cord regions (cervical and lumbar)…

Fig. 5 Brain-to-blood efflux of PrPc after icv injection. Half-time clearance from brain was 15.7 min. Inset shows that inclusion of unlabeled PrPc in the icv injection increased retention of radioactively labeled PrPc by brain, demonstrating a saturable component
Does aluminum in vaccines have a more sinister plot that is stated?

Differential effect of aluminum on the blood-brain barrier transport of peptides, technetium and albumin.


Aluminum is a neurotoxin capable of altering membrane structure and function. We investigated whether aluminum also can affect saturable transport across membranes using the blood-brain barrier as our model. Mice were given i.p. or i.v. aluminum (up to 100 mg/kg) as the chloride salt and the disappearance from the brain of several centrally administered substances was measured. We found that aluminum rapidly and profoundly inhibited the saturable system that transports the small, N-tyrosinated peptides Tyr-MIF-1 and the enkephalins from the brain to the blood by acting as a noncompetitive inhibitor. In contrast, the disappearance from the brain of technetium pertechnetate (a substance also transported out of the brain by a different saturable system), albumin or D-Tyr-MIF-1 (a stereoisomer of Tyr-MIF-1 that was confirmed not to be transported by the carrier system) was not affected by aluminum. Aluminum also did not alter either the saturable or nonsaturable component of the uptake of Tyr-MIF-1 by erythrocytes. These findings suggest that one mechanism by which aluminum may induce neurotoxicity is by selective alteration of the transport systems of the blood-brain barrier.



An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body’s opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one containing leucine (“leu”), and the other containing mathione (“met”). Both are products of the proenkephalin gene.


Endogenous opioid peptides

There are three well-characterized families of opioid peptides produced by the body: enkephalins, endorphines, and dynorphins. The met-enkephalin peptide sequence is coded for by the enkephalin gene; the leu-enkephalin peptide sequence is coded for by both the enkephalin gene and the dynorphin gene.[3] The proopiomelanocortin gene (POMC) also contains the met-enkephalin sequence on the N-terminus of beta-endorphin, but the endorphin peptide is not processed into enkephalin.

Enkephalin receptor

Main article: Opioid recepter
The receptors for enkephalin are the delta opioid receptors. Opioid receptors are a group of G-protein-coupled receptors, with other opioids as ligands as well. The other endogenous opioids are dynorphins (that bind to kappa receptors), endorphines (mu receptors), endomorphins, and nociceptin/orphanin FQ. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs).


Endomorphins, Met-Enkephalin, Tyr-MIF-1, and the P-glycoprotein Efflux System


The P-glycoprotein (P-gp) transport system, responsible for the efflux of many therapeutic drugs out of the brain, recently has been shown to transport the endogenous brain opiate endorphin. We used P-gp knockout mice (Mdr1a) and their controls to determine where P-gp is involved in the saturable efflux systems of four other endogenous opiate-modulating peptides across the blood-brain barrier (BBB). After injection of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), Met-enkephalin (Tyr-Gly-Gly-Phe-Met-OH), and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) into the lateral ventricle of the mouse brain, residual radioactivity was measured at 0, 2, 5, 10, and 20 min later. The results showed no difference in the disappearance of any of these peptides from the brains of knockout mice compared with their controls. This demonstrates that unlike endorphin and morphine, P-gp does not seem to be required for the brain-to-blood transport of the endomorphins, Met-enkephalin, or Tyr-MIF-1 across the BBB.


  • This work was supported by the United States Army Medical Research Acquisition Activity (DAMD17-00-0113) and the Department of Veterans Affairs.



Endorphins (“endogenous morphine”) are endogenous opioid inhibitory neuropeptides. They are produced by the central nervous system and pituitary gland. The term implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean “a morphine-like substance originating from within the body.”[1]


Opioid neuropeptides were first discovered in 1974 by two independent groups of investigators:

  • John Hughes and Hans Kosterlitz of Scotland isolated — from the brain of a pig — what some called enkephalins (from the Greek εγκέφαλος, cerebrum).[2][3]
  • Around the same time, in a calf brain, Rabi Simantov and Solomon H. Snyder of the United States found[4] what Eric Simon (who independently discovered opioid receptors in vertebral brains) later termed “endorphin” by an abreviation of of “endogenous morphine”, meaning “morphine produced naturally in the body”.[1] Importantly, recent studies have demonstrated that human and diverse animal tissues are in fact capable of producing morphine itself, which is not a peptide.[5][6]

Mechanism of action

Beta-endorphin (β-endorphin) is released into blood from the pituitary gland and into the spinal cord and brain from hypothalamic neurons. The β-endorphin that is released into the blood cannot enter the brain in large quantities because of the blood-brain barrier, so the physiological importance of the β-endorphin that can be measured in the blood is far from clear. β-endorphin is a cleavage product of pro-opiomelanocortin (POMC), which is also the precursor hormone for adrenocorticotrophic hormone (ACTH). The behavioural effects of β-endorphin is exerted by its actions in the brain and spinal cord, and it is presumed that the hypothalamic neurons are the major source of β-endorphin at those sites. In situations where the level of ACTH is increased (e.g., Cushing’s disease), the level of β-endorphin also increases slightly.

β-endorphin has the highest affinity for the μ1 opioid receptor, slightly lower affinity for the μ2 and δ opioid receptors, and low affinity for the κ1 opioid receptors. μ-Opioid receptors are the main receptor through which morphine acts. In the classical sense, μ opioid receptors are presynaptic, and inhibit neurotransmitter release. Through that mechanism, they inhibit the release of the inhibitory neurotransmitter GABA, and disinhibit the dopamine pathways, causing more dopamine to be released. By hijacking this process, exogenous opioids cause inappropriate dopamine release, and can lead to aberrant synaptic plasticity, which can cause dependency. Opioid receptors have many other and more important roles in the brain and periphery; however, modulating pain, cardiac, gastric and vascular function as well as possibly panic and satiation. Also, receptors are often found at postsynaptic locations as well as at presynaptic locations…


Morphine preconditioning reduces lipopolysaccharide and interferon-γ-induced mouse microglial cell injury via δ1 opioid receptor activation


Microglial cells play an important role in the inflammatory response of a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to protect microglial cells. Here, we showed that incubation of the C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-γ (IFNγ) induced cytotoxicity as assessed by the amount of lactate dehydrogenase (LDH) released from the cells. Preconditioning the cells with morphine for 30 min concentration-dependently reduced LPS plus IFNγ-induced cell injury. This morphine preconditioning effect was abolished by naloxone, a general opioid receptor antagonist, by naltrindole, a selective δ opioid receptor antagonist and by 7-benzylidenenaltrexone maleate, a selective δ1 opioid receptor antagonist. However, this protective effect was not affected by β-funaltrexamine, a selective μ opioid receptor antagonist, nor-binaltorphimine, a selective κ opioid receptor antagonist or naltriben, a selective δ2 opioid receptor antagonist. LPS plus IFNγ induced the expression of inducible nitric oxide synthase (iNOS), which was not affected by morphine preconditioning. Our results suggest that morphine induced a preconditioning effect in microglial cells. This effect may be mediated by δ1 opioid receptors and may not be through inhibiting the expression of iNOS, a potentially harmful protein.



Prion peptide PrP106-126 induces inducible nitric oxide synthase (iNOS) and proinflammatory cytokine gene expression through the activation of NF-kB in macrophage cells

The inflammatory response in prion diseases is dominated by microglia activation. The molecular mechanisms that lie behind this inflammatory process are not very well understood. In the present study, we examined the activation of nuclear factor-kappa B (NF-κB) upon exposure to PrP106-126 and its role in PrP106-126-induced upregulation of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6) in Ana-1 macrophages. The results showed that iNOS and proinflammatory cytokine release was significantly elevated in Ana-1 macrophages upon exposure to PrP106-126; that PrP106-126 treatment led to a significant NF-κB activation; that proinflammatory cytokines gene expression was elevated in macrophages upon exposure to PrP106-126; and that NF-κB inhibition significantly abrogated PrP106-126-induced upregulation of iNOS and inflammatory cytokine mRNA expression. These results suggest that treatment with neurotoxic prion peptides leads to the activation of transcription factor NF-κB, which in turn stimulates gene expression of iNOS and proinflammatory cytokines in Ana-1 macrophages.



The Transcription Factor Nuclear Factor-kappa B and Cancer


Since the discovery of nuclear factor-kappa B (NF-κB) in 1986, many studies have been conducted showing the link between the NF-κB signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF-κB. Three NF-κB activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation-induced IκB degradation and depends mainly on IKKβ activity. The second (the alternative pathway), leads to selective activation of p52:RelB dimers by inducing the processing of the NF-κB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKKα homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-κB acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-κB, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-κB in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-κB activation is closely related to different cancers, and finally the potential target of NF-κB as cancer therapy.



Nuclear factor kappa B (NF-κB) in multiple sclerosis pathology


• NF-κB signaling in MS patients and animal models of MS.
NF-κB signaling controls peripheral immune activation at multiple levels.
NF-κB controls inflammatory responses locally in the CNS.
• NF-κB as a therapeutic target for the treatment of MS.

The nuclear factor kappa B (NF-κB) signaling cascade plays a critical role in the regulation of immune and inflammatory responses and has been implicated in the pathogenesis of autoimmune demyelinating diseases such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the main animal model of MS. NF-κB is essential for peripheral immune cell activation and the induction of pathology, but also plays crucial roles in resident cells of the central nervous system (CNS) during disease development. Here we review recent evidence clarifying the role of NF-κB in the different cell compartments contributing to MS pathology and its implications for the development of therapeutic strategies for the treatment of MS and other demyelinating pathologies of the CNS.



NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet radiation, oxidized LDL, and bacterial or viral antigens.[1][2][3][4][5] NF-κB plays a key role in regulating the immune response to infection (k light chains are critical components of immunoglobulins). Incorrect regulation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.[6][7][8][9][10]

In brief, NF-κB can be understood to be a protein responsible for cytokine production and cell survival.


All proteins of the NF-κB family share a Rel homology domain in their N-terminus. A subfamily of NF-κB proteins, including RelA, RelB, and c-Rel, have a transactivation domain in their C-termini. In contrast, the NF-κB1 and NF-κB2 proteins are synthesized as large precursors, p105, and p100, which undergo processing to generate the mature NF-κB subunits, p50 and p52, respectively. The processing of p105 and p100 is mediated by the ubiquitin/proteasome pathway and involves selective degradation of their C-terminal region containing ankyrin repeats. Whereas the generation of p52 from p100 is a tightly regulated process, p50 is produced from constitutive processing of p105.[12][13] The p50 and p52 proteins have no intrinsic ability to activate transcription and thus have been proposed to act as transcriptional repressors when binding κB elements as homodimers.[14][15] Indeed, this confounds the interpretation of p105-knockout studies, where the genetic manipulation is removing an IκB (full-length p105) and a likely repressor (p50 homodimers) in addition to a transcriptional activator (the RelA-p50 heterodimer).


NF-κB family members share structural homology with the retroviral oncoprotein v-Rel, resulting in their classification as NF-κB/Rel proteins.[1]

There are five proteins in the mammalian NF-κB family:[16]

Species distribution and evolution

In addition to mammals, NF-κB is found in a number of simple animals as well.[17] These include cnidarians (such as sea anemones, coral and hydra), porifera (sponges), the single-celled eukaryote Capsaspora owczarzaki and insects (such as moths, mosquitoes, and fruit flies). The sequencing of the genomes of the mosquitoes A. aegypti and A. gambiae, and the fruitfly D. melangaster has allowed comparative genetic and evolutionary studies on NF-κB. In those insect species, activation of NF-κB is triggered by the Toll pathway (which evolved independently in insects and mammals) and by the Imd (immune deficiency) pathway.[18]

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses



NF-κB (green) heterodimerizes with RelB (cyan) to form a ternary complex with DNA (orange) that promotes gene transcription.[19]

NF-κB is important in regulating cellular responses because it belongs to the category of “rapid-acting” primary transcription factors, i.e., transcription factors that are present in cells in an inactive state and do not require new protein synthesis in order to become activated (other members of this family include transcription factors such as c-Jun, STATs, and nuclear hormone receptors). This allows NF-κB to be a first responder to harmful cellular stimuli. Known inducers of NF-κB activity are highly variable and include reactive oxygen species (ROS), tumor necrosis factor alpha (TNFa), interleukin 1-beta (IL1β), bacterial lipopolysaccharides (LPS), isoproterenol, cocaine, and ionizing radiation.[20]

Receptor activator of NF-κB (RANK), which is a type of TNFR, is a central activator of NF-κB. Osteoprotegerin (OPG), which is a decoy receptor homolog for RANK ligand, inhibits RANK by binding to RANKL, and, thus, osteoprotegerin is tightly involved in regulating NF-κB activation.[21]

Many bacterial products and stimulation of a wide variety of cell-surface receptors lead to NF-κB activation and fairly rapid changes in gene expression.[1] The identification of Toll-like receptors(TLRs) as specific pattern recognition molecules and the finding that stimulation of TLRs leads to activation of NF-κB improved our understanding of how different pathogens activate NF-κB. For example, studies have identified TLR4 as the receptor for the LPS component of Gram-negative bacteria.[22] TLRs are key regulators of both innate and adaptive immune responses.[23]

Unlike RelA, RelB, and c-Rel, the p50 and p52 NF-κB subunits do not contain transactivation domains in their C terminal halves. Nevertheless, the p50 and p52 NF-κB members play critical roles in modulating the specificity of NF-κB function. Although homodimers of p50 and p52 are, in general, repressors of κB site transcription, both p50 and p52 participate in target gene transactivation by forming heterodimers with RelA, RelB, or c-Rel.[24] In addition, p50 and p52 homodimers also bind to the nuclear protein Bcl-3, and such complexes can function as transcriptional activators.[25][26][27]


In unstimulated cells, the NF-κB dimers are sequestered in the cytoplasm by a family of inhibitors, called IκBs (Inhibitor of κB), which are proteins that contain multiple copies of a sequence called ankyrin repeats. By virtue of their ankyrin repeat domains, the IκB proteins mask the nuclear localization signals (NLS) of NF-κB proteins and keep them sequestered in an inactive state in the cytoplasm.[28]

IκBs are a family of related proteins that have an N-terminal regulatory domain, followed by six or more ankyrin repeats and a PEST domain near their C terminus. Although the IκB family consists of IκBα, IκBβ, IκBε, and Bcl-3, the best-studied and major IκB protein is IκBα. Due to the presence of ankyrin repeats in their C-terminal halves, p105 and p100 also function as IκB proteins. The c-terminal half of p100, that is often referred to as IκBδ, also functions as an inhibitor.[29][30] IκBδ degradation in response to developmental stimuli, such as those transduced through LTβR, potentiate NF-κB dimer activation in a NIK dependent non-canonical pathway.[29][31]

Activation of the NF-κB is initiated by the signal-induced degradation of IκB proteins. This occurs primarily via activation of a kinase called the IκB kinase (IKK). IKK is composed of a heterodimer of the catalytic IKKα and IKKβ subunits and a “master” regulatory protein termed NEMO (NF-κB essential modulator) or IKK gamma. When activated by signals, usually coming from the outside of the cell, the IκB kinase phosphorylates two serine residues located in an IκB regulatory domain. When phosphorylated on these serines (e.g., serines 32 and 36 in human IκBα), the IκB inhibitor molecules are modified by a process called ubiquitination, which then leads them to be degraded by a cell structure called the proteasome.

With the degradation of IκB, the NF-κB complex is then freed to enter the nucleus where it can ‘turn on’ the expression of specific genes that have DNA-binding sites for NF-κB nearby. The activation of these genes by NF-κB then leads to the given physiological response, for example, an inflammatory or immune response, a cell survival response, or cellular proliferation. NF-κB turns on expression of its own repressor, IκBα. The newly synthesized IκBα then re-inhibits NF-κB and, thus, forms an auto feedback loop, which results in oscillating levels of NF-κB activity.[32] In addition, several viruses, including the AIDS virus HIV, have binding sites for NF-κB that controls the expression of viral genes, which in turn contribute to viral replication or viral pathogenicity. In the case of HIV-1, activation of NF-κB may, at least in part, be involved in activation of the virus from a latent, inactive state.[33] YopP is a factor secreted by Yersinia pestis, the causative agent of plague, that prevents the ubiquitination of IκB. This causes this pathogen to effectively inhibit the NF-κB pathway and thus block the immune response of a human infected with Yersinia.[34]

Inhibitors of NF-κB activity

Concerning known protein inhibitors of NF-κB activity, one of them is IFRD1, which represses the activity of NF-κB p65 by enhancing the HDAC-mediated deacetylation of the p65 subunit at lysine 310, by favoring the recruitment of HDAC3 to p65. In fact IFRD1 forms trimolecular complexes with p65 and HDAC3.[35][36]


A select set of cell-differentiating or developmental stimuli, such as lymphotoxin-α, BAFF or RANKL, activate the non-canonical NF-κB pathway to induce NF-κB/RelB:p52 dimer in the nucleus. In this pathway, activation of the NF-κB inducing kinase (NIK) upon receptor ligation led to the phosphorylation and subsequent proteasomal processing of the NF-κB2 precursor protein p100 into mature p52 subunit in an IKK1/IKKa dependent manner. Then p52 dimerizes with RelB to appear as a nuclear RelB:p52 DNA binding activity and regulate a distinct class of genes.[37] In contrast to the canonical signaling that relies upon NEMO-IKK2 mediated degradation of IκBα, -β, -ε, the non-canonical signaling critically depends on NIK mediated processing of p100 into p52. Given their distinct regulations, these two pathways were thought to be independent of each other. However, recent analyses revealed that synthesis of the constituents of the non-canonical pathway, viz RelB and p52, is controlled by the canonical IKK2-IκB-RelA:p50 signaling.[38] Moreover, generation of the canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are also mechanistically interlinked.[38] These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non-canonical pathway.

In immunity

NF-κB is a major transcription factor that regulates genes responsible for both the innate and adaptive immune response. Upon activation of either the T- or B-cell receptor, NF-κB becomes activated through distinct signaling components. Upon ligation of the T-cell receptor, protein kinase Lck is recruited and phosphorylates the ITAMs of the CD3 cytoplasmic tail. ZAP70 is then recruited to the phosphorylated ITAMs and helps recruit LAT and PLC-γ, which causes activation of PKC. Through a cascade of phosphorylation events, the kinase complex is activated and NF-κB is able to enter the nucleus to upregulate genes involved in T-cell development, maturation, and proliferation.[39]

In the nervous system

In addition to roles in mediating cell survival, studies by Mark Mattson and others have shown that NF-κB has diverse functions in the nervous system including roles in plasticity, learning, and memory. In addition to stimuli that activate NF-κB in other tissues, NF-κB in the nervous system can be activated by Growth Factors (BDNF, NGF) and synaptic transmission such as glutamate.[7] These activators of NF-κB in the nervous system all converge upon the IKK complex and the canonical pathway.

Recently there has been a great deal of interest in the role of NF-κB in the nervous system. Current studies suggest that NF-κB is important for learning and memory in multiple organisms including crabs,[9][10] fruit flies,[40] and mice.[7][8] NF-κB may regulate learning and memory in part by modulating synaptic plasticity,[6][41] synapse function,[40][42][43] as well as by regulating the growth of dendrites[44] and dendritic spines.[43]

Genes that have NF-κB binding sites are shown to have increased expression following learning,[8] suggesting that the transcriptional targets of NF-κB in the nervous system are important for plasticity. Many NF-κB target genes that may be important for plasticity and learning include growth factors (BDNF, NGF)[45] cytokines (TNF-alpha, TNFR)[46] and kinases (PKAc).[41]

Despite the functional evidence for a role for Rel-family transcription factors in the nervous system, it is still not clear that the neurological effects of NF-κB reflect transcriptional activation in neurons. Most manipulations and assays are performed in the mixed-cell environments found in vivo, in “neuronal” cell cultures that contain significant numbers of glia, or in tumor-derived “neuronal” cell lines. When transfections or other manipulations have been targeted specifically at neurons, the endpoints measured are typically electrophysiology or other parameters far removed from gene transcription. Careful tests of NF-κB-dependent transcription in highly purified cultures of neurons generally show little to no NF-κB activity.[47][48] Some of the reports of NF-κB in neurons appear to have been an artifact of antibody nonspecificity.[49] Of course, artifacts of cell culture—e.g., removal of neurons from the influence of glia—could create spurious results as well. But this has been addressed in at least two coculture approaches. Moerman et al.[50] used a coculture format whereby neurons and glia could be separated after treatment for EMSA analysis, and they found that the NF-κB induced by glutamatergic stimuli was restricted to glia (and, intriguingly, only glia that had been in the presence of neurons for 48 hours). The same investigators explored the issue in another approach, utilizing neurons from an NF-κB reporter transgenic mouse cultured with wild-type glia; glutamatergic stimuli again failed to activate in neurons.[51] Some of the DNA-binding activity noted under certain conditions (particularly that reported as constitutive) appears to result from Sp3 and Sp4 binding to a subset of κB enhancer sequences in neurons.[52] This activity is actually inhibited by glutamate and other conditions that elevate intraneuronal calcium. In the final analysis, the role of NF-κB in neurons remains opaque due to the difficulty of measuring transcription in cells that are simultaneously identified for type. Certainly, learning and memory could be influenced by transcriptional changes in astrocytes and other glial elements. And it should be considered that there could be mechanistic effects of NF-κB aside from direct transactivation of genes.

Clinical significance

Overview of signal transduction pathways involved in apoptosis.


NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated NF-κB: that is, NF-κB is constitutively active. Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis.

Defects in NF-κB results in increased susceptibility to apoptosis leading to increased cell death. This is because NF-κB regulates anti-apoptotic genes especially the TRAF1 and TRAF2 and, therefore, checks the activities of the caspase family of enzymes, which are central to most apoptotic processes.[53]

In tumor cells, NF-κB is active either due to mutations in genes encoding the NF-κB transcription factors themselves or in genes that control NF-κB activity (such as IκB genes); in addition, some tumor cells secrete factors that cause NF-κB to become active. Blocking NF-κB can cause tumor cells to stop proliferating, to die, or to become more sensitive to the action of anti-tumor agents. Thus, NF-κB is the subject of much active research among pharmaceutical companies as a target for anti-cancer therapy.[54]

However, caution should be exercised when considering anti-NF-κB activity as a broad therapeutic strategy in cancer therapy, even though convincing experimental data have identified NF-κB as a critical promoter of cancer development, creating a solid rationale for the development of antitumor therapy that suppresses NF-κB activity. Data have also shown that NF-κB activity enhances tumor cell sensitivity to apoptosis and senescence. In addition, it has been shown that canonical NF-κB is a Fas transcription activator and the alternative NF-κB is a Fas transcription repressor.[55] Therefore, NF-κB promotes Fas-mediated apoptosis in cancer cells, and thus inhibition of NF-κB may suppress Fas-mediated apoptosis to impair host immune cell-mediated tumor suppression.


Because NF-κB controls many genes involved in inflammation, it is not surprising that NF-κB is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, atherosclerosis[56] and others. It is important to note though, that elevation of some NF-κB inhibitors, such as osteoprotegerin (OPG), are associated with elevated mortality, especially from cardiovascular diseases.[57][58] Elevated NF-κB has also been associated with schizophrenia.[59] Recently, NF-κB activation has been suggested as a possible molecular mechanism for the catabolic effects of cigarette smoke in skeletal muscle and sarcopenia.[60]

Non-drug inhibitors

Many natural products (including anti-oxidants) that have been promoted to have anti-cancer and anti-inflammatory activity have also been shown to inhibit NF-κB.[61][62] There is a controversial US patent (US patent 6,410,516)[63] that applies to the discovery and use of agents that can block NF-κB for therapeutic purposes. This patent is involved in several lawsuits, including Ariad v. Lilly. Recent work by Karin,[64] Ben-Neriah[65] and others has highlighted the importance of the connection between NF-κB, inflammation, and cancer, and underscored the value of therapies that regulate the activity of NF-κB.[66]

Extracts from a number of herbs and dietary plants are efficient inhibitors of NF-κB activation in vitro.[67][68][69]

The circumsporozoite protein of Plasmodium falciparum has been shown to be an inhibitor of NF-κB.[70]

As a drug target

Aberrant activation of NF-κB is frequently observed in many cancers. Moreover, suppression of NF-κB limits the proliferation of cancer cells. In addition, NF-κB is a key player in the inflammatory response. Hence methods of inhibiting NF-κB signaling has potential therapeutic application in cancer and inflammatory diseases.[71][72]

The discovery that activation of NF-κB nuclear translocation can be separated from the elevation of oxidant stress[73] gives an important hint to the development of strategies for NF-κB inhibition.

A new drug called denosumab acts to raise bone mineral density and reduce fracture rates in many patient sub-groups by inhibiting RANKL. RANKL acts through its receptor RANK, which in turn promotes NF-κB,[74] RANKL normally works by enabling the differentiation of osteoclasts from monocytes.

Disulfiram, olmesartan and dithiocarbamates can inhibit the nuclear factor-κB (NF-κB) signaling cascade.[75]

Anatabine’s antiinflammatory effects are claimed to result from modulation of NF-κB activity.[76] However the studies purporting its benefit use abnormally high doses in the millimolar range (similar to the extracellular potassium concentration), which are unlikely to be achieved in humans.



Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.[1]

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S  proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappaB (NF-kB) protein complex. NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions; over 200 known genes are targets of NF-κB in various cell types, under specific conditions. Inappropriate activation of NF-κB has been associated with a number of inflammatory diseases while persistent inhibition of NF-κB leads to inappropriate immune cell development or delayed cell growth.[2]


Signal Transduction Through Prion Protein

The cellular prion protein PrPc is a glycosylphosphatidylinositol-anchored cell-surface protein whose biological function is unclear. We used the murine 1C11 neuronal differentiation model to search for PrPc-dependent signal transduction through antibody-mediated cross-linking. A caveolin-1–dependent coupling of PrPc to the tyrosine kinase Fyn was observed. Clathrin might also contribute to this coupling. The ability of the 1C11 cell line to trigger PrPc-dependent Fyn activation was restricted to its fully differentiated serotonergic or noradrenergic progenies. Moreover, the signaling activity of PrPc occurred mainly at neurites. Thus, PrPc may be a signal transduction protein.

Science 15 September 2000:
Vol. 289
no. 5486 pp. 19251928

A cellular gene encodes scrapie PrP 27-30 protein.


A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein. Southern blotting with PrP cDNA revealed a single gene with the same restriction patterns in normal and scrapie-infected brain DNA. A single PrP-related gene was also detected in murine and human DNA. PrP-related mRNA was found at similar levels in normal and scrapie-infected hamster brain, as well as in many other normal tissues. Using antisera against PrP 27-30, a PrP-related protein was detected in crude extracts of infected brain and to a lesser extent in extracts of normal brain. Proteinase K digestion yielded PrP 27-30 in infected brain extract, but completely degraded the PrP-related protein in normal brain extract. No PrP-related nucleic acids were found in purified preparations of scrapie prions, indicating that PrP 27-30 is not encoded by a nucleic acid carried within the infectious particles.



Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions


Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions of neurodegenerative diseases; however, the precise mechanisms by which MSCs migrate remain to be elucidated. In this study, we carried out an in vitro migration assay to investigate the chemoattractive factors for MSCs in the brains of prion-infected mice. The migration of immortalized human MSCs (hMSCs) was reduced by their pretreatment with antibodies against the chemokine receptors, CCR3, CCR5, CXCR3, and CXCR4 and by pretreatment of brain extracts of prion-infected mice with antibodies against the corresponding ligands, suggesting the involvement of these receptors, and their ligands in the migration of hMSCs. In agreement with the results of an in vitro migration assay, hMSCs in the corpus callosum, which are considered to be migrating from the transplanted area toward brain lesions of prion-infected mice, expressed CCR3, CCR5, CXCR3, and CXCR4. The combined in vitro and in vivo analyses suggest that CCR3, CCR5, CXCR3, and CXCR4, and their corresponding ligands are involved in the migration of hMSCs to the brain lesions caused by prion propagation. In addition, hMSCs that had migrated to the right hippocampus of prion-infected mice expressed CCR1, CX3CR1, and CXCR4, implying the involvement of these chemokine receptors in hMSC functions after chemotactic migration. Further elucidation of the mechanisms that underlie the migration of MSCs may provide useful information regarding application of MSCs to the treatment of prion diseases.


Prion diseases are fatal neurodegenerative disorders in humans and animals that are characterized by the accumulation of a disease-specific isoform of the prion protein (PrPSc), astrocytosis, microglial activation, spongiosis, and neuronal cell death in the central nervous system (CNS). Although the etiology of the diseases is not clear, conversion of the normal prion protein to PrPSc plays a key role in the neuropathological changes (44). Therefore, compounds that inhibit PrPSc formation are considered as therapeutic candidates of the diseases, and many compounds have been reported to inhibit PrPSc formation in cell cultures and cell-free systems (reviewed in reference 56). However, only a few of these inhibitors, such as amphotericin B and its derivative (13), pentosan polysulfate (14), porphyrin derivatives (27), certain amyloidophilic compounds (25), and FK506 (37) have been reported to prolong the survival of prion-infected mice even when administered in the middle-late stage of infection but still before clinical onset. We recently reported that intraventricular infusion of anti-PrP antibodies (50) slowed down the progression of the disease even when initiated just after clinical onset. However, in addition to inhibition of PrPSc formation, the protection of neurons or restoration of degenerated neurons is thought to be important for functional recovery.

Bone marrow-derived mesenchymal stem cells (MSCs) differentiate into cells of mesodermal origin such as adipocytes, osteoblasts, and endothelial and muscle cells (41, 43). In addition, MSCs are known to transdifferentiate into neuronal and glial cells. MSCs have been shown to migrate to damaged neuronal tissues and to alleviate the deficits in experimental animal models of cerebral ischemia (10), spinal cord injury (20), Parkinson’s disease (19, 33), and amyotrophic lateral sclerosis (59). MSCs also secrete various neurotrophic factors that may protect neuronal tissues from degradations, as well as stimulate the activity of endogenous neural stem cells (38). Therefore, despite their mesodermal origin, MSCs are considered to be a candidate for cell-mediated therapy for neurodegenerative diseases. One of the characteristics of MSCs is their migration to brain lesions caused by neurodegenerative diseases, including prion diseases (10, 19, 39, 51). This feature may be of further use for cell-mediated therapy of neurodegenerative diseases, particularly for prion diseases, Multiple sclerosis and Alzheimer’s disease, which have diffuse pathological lesions.

Since many cytokines, chemokines, and adhesion molecules are involved in the homing of immune cells (9, 36, 53), evidence that a variety of chemokines and growth factors, as well as their cognate receptors, have a pivotal role in the migration of MSCs has been accumulated. These factors include CXCL12 and its receptor CXCR4 (30, 40; reviewed in reference 52), CCL2 (15, 62, 66), CCL3 (62), interleukin-8 (48, 62), hepatocyte growth factor (16), platelet-derived growth factor AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), CCL5 and CCL22 (42), and integrin β1 (23). Regarding the migration of MSCs to injury in the CNS, the involvement of CCL2 (61), CXCL12/CXCR4, and CX3CL1/CX3CR1 (24) has been reported. However, knowledge of the mechanism by which MSCs migrate to pathological lesions of neurodegenerative diseases is insufficient, and further efforts are required to elucidate this mechanism.

We recently reported that human MSCs (hMSCs) migrate to CNS lesions and prolong the survival of mice infected with prions (51). In the present study, we investigated factors that are involved in the migration of hMSCs to brain lesions of prion diseases.



To say that the body is one giant communication system is an understatement. The expression of genes and the ability for host cells to operate normally and to chemically call for help when faced with an antigen is esential to health. As discussed above, these prion interferors with the interferon and other defensive signaling processes must be injected to bypass the mucosus and the skin. This can only be accomplished through innoculation and vaccination.

The introduction of foreign proteins and DNA/RNA into the otherwise healthy body is certainly described here as the cause of most disease states in modern times. And from the time that this interferon was discovered, these psychopathic scientists have been working overtime to prevent our bodies from being able to fight what they inject.

What you have just read is the cause and cure for AIDS, cancers, dementias, and a host of other modern medically-induced disease states that revolve around prion infection and misfolding of the signal processing of the body. It is not so much a cure as an acknowledgement of the cause, for when disease is purposefully caused, the word cure seems trivial in practice, and allows the culprits to literally get away with murder.

It was caused by them…

Will we sit by helplessly and hope for a cure to these purposefully caused diseases by the very perpetrators of them?

Isn’t that the American way though?

For as we wait, they merely perfect their science of biological aggression and warfare…

(Note: all unlinked data as descriptions above from Wikipedia, which are well-sourced within that site.)


–Clint Richardson (
–Thursday, December 4rth, 2014

Leave a comment


  1. Mary E Bailey

     /  December 4, 2014

    Wow Clint! No ‘co-inky-dink’ that serendipitous synchronicity abounds amongst sharers of information for the betterment of all (((<3))) Please see what Dr Jennifer Daniels has to say about spirochetes & therefore syphilis as basically being the same as prion disease, acquired in the same way, when any injection is administered! She was not allowed to treat for or even acknowledge the existence of "S" even though it was in Every sample from Everyone! A case of frightening semantics again and even more frightening intentionality?

  2. Well, My Friend,

    You managed to do it again. You pulled together what might seem to be unrelated material to weave the Nexus that pulls together many open topics in at least 5 of my books. By inference you gave me the mechanism by which the brain operates its trash removal system that is either not known, or occulted by those who get government grants to study it. Since I get no grants I will only share this knowledge in my next books. We of the disenfranchised have to eat.

    Of special note are the connections between common pharmaceutical drugs and disequilibrium in the body that can be permanent. This was planned. They know what they are doing because people like you and I can figure it out.

    I absolutely love your notion of the Cell-phone.

    I was told by former military that I worked with in telecommunications that one of the primary objectives in warfare is to take out command and control by disrupting communications. If you can’t talk to your troops or your country then you cannot protect yourself or coordinate counter-offensives. It seems that they have succeeded in this phase. Your citation of chromosome number 1 shows me that just the MTHFR (I’m not swearing) genes are not the only ones that they targeted for destruction to enslave us to their drugs and alternative medicine supplements. Yes, both of them are in on this.

    It will help to advance your work and our understanding to factor in the Secrets of the Dead episode from PBS on the Plague (Yersinia cited in your references by the way with respect to AIDS) and the delta 32 mutation that is shown in that episode to prevent T-cells from being infected by HIV. Keeping in mind that Rh factor might be a player as well.

    All in all your sheer volume of absolutely connected, yet overwhelming data, makes me Giddy.

    Not a joke. I am doing a transcription of a USDA publication from 1898 that refers to Turn-sick disease called Gid, from the Gid Bladderworm infection. It seems that a tapeworm growing in different parts of a sheep’s brain can cause specific behaviors. Now in the world of Hulda Clark and Hegner (1936) those English worms might have brought the bacteria that hosted the virus that caused the Scrapie that lived in the brains that Jack built. As we chase these processes down to the molecular level we have to take a look up from the microscope some times to get a clear sense of where we came from.

    So that there is no enthusiasm generated from the intervention of bone marrow replacement to rescue those from dread disease: Always keep in mind that my theory is that Who we are resides in our White Blood Cells. Therefore, if a total rewrite of Us is accomplished by gutting the bone marrow and replacing it with that of a foreigner then we cease to exist. But then, wasn’t that the plan all along?

  3. Dear Clint…
    In the late 1800’s there was the discovery of the Rostta Stone in Egypt.After Moses split the scene and Yutmoses got a free chariot wash for himself…
    I believe the Egyptians were cursed with diseases.And overlooked was the Egyptomaina that transformed society a the turn of the century through the 20’s and 30’s(google image cleopatramania) and have a look see.
    There is also a book called Egyptomania By Bob Brier and Zahi Hawass to chronicle this time.For some reason the Egyptian Craze that overtook the world isn’t reall a part of our collective memory of past events.
    It was very big and based on discoveries ever since Napoleon came across the Egyptian ruins and most importantly the Rosetta Stone.They make no mention inthe abov e mentioned books of Aleister Crowley and jetsetters (OK no jets then …The oceanliner crowd) were sleeping in tombs extremely promiscuous and on to extremeley bizzare behavior.
    Many of the crazed would end up being bombed by (etc)the “Nazi’s” or the “allies” and had a horrible end.
    Shortly before all this the Rosetta Stone was discovered and in time was deciphered and I’m going to quote some text here…
    Europeans had apparently lived for thousands of years maintaining a similar lifestyle and very few new inventions, living in villages and farm land, using a horse and cart. The Rosetta Stone was found in 1799 and during the 1800’s [19th century] the word ‘SCIENTIST’ is used for the first time, coined by William Whewell in 1833. During the 1800’s the following inventions were introduced to the 19th century giving birth to the industrial revolution:

    Steel, petroleum products, machinery, internal combustion engines, motor vehicles, sewing machines, telephone, typewriter, light bulbs, steam locomotives, electricity, stethoscope, fiber optics, elevator, plastics, phonograph, smokeless gunpowder, dynamite, motion pictures, surgical anaesthesia , steam boat, rubber technology, water turbine, microphone, fuel cell, saxophone, hydraulic crane, steam powered submarine, incandescent lamp, standard universal time, contact lens, brown paper bags, dish washer, pneumatic tyre, machine gun, thermos flask, x-ray machine, weapons of mass destruction….a fuller list would take up the entire page.—

    There wasn’t just an explosion in the sciences either, there was a new understanding of esoteric knowledge and people such as the Russian noble – Madam Blavatsky, Edgar Cayce, Aleister Crowley with his Enochian magick and ‘Astarie children’ and the birthing of the new age and the channelling of ‘ascended masters’ – the gods and priests of ancient Kemet. The Freemasons and other cults referred to Kemet knowledge as, ‘mysteries’ due to the complexity and diversity of the material; but the Egyptian’s themselves never referred to this knowledge as ‘mysterious’ they simply called them, ‘sciences’. The word ‘scientist’ was used for the first time in the 1800’s by Europeans. There were no hidden mystery schools in Egypt, only temple Universities available even to foreign students. The classical Greek period owes most of its knowledge to ancient Egypt which is clear when you read the accounts of Plato and the many others who attended Kemet universities. —-
    —————–Also around this time the word Technology was introduced as science.
    A 1910 Book The marvels beyond science : (L’occultisme hier et aujourd’hui; le merveilleux préscientifique) : being a record of progress made in the reduction of occult phenomena to a scientific basis (1910)
    Author: Grasset, J. (Joseph), 1849-1918; Tubeuf, René Jacques, tr
    Subject: Occultism; Parapsychology; Telepathy; Clairvoyance; Occultism
    Publisher: New York ; Funk & Wagnalls company
    Language: English
    Call number: 001460732
    Digitizing sponsor: Open Knowledge Commons and Harvard Medical School
    Book contributor: Francis A. Countway Library of Medicine
    Collection: medicalheritagelibrary; francisacountwaylibrary; americana
    One cannot overlook the influences that surrounded this explosion in technoogy mirroring what has happened in past civilizations.
    The treasures in Egypt have have been loaded with prions.Maybe that’s why people left it alone for thousands of years?
    “Sex in Ancient Egypt” Documentary | Extraordinary People

    According to the History Channel there are some things about the Egyptians that have been kept from the public till now.Apparently they were some kinky cats! What better way to get prion exposure ?
    There has obviously been a massive exponential spike in “Technology”since that time and it correlates with the tales of the Archons of Atlantis.
    I’ll leave you with a timeless Sword and Sandal Classic cult movie for your consideration.
    Atlantis, the Lost Continent is a 1961 science fiction film, directed by George Pal and starring Anthony Hall aka: Sal Ponti,[1] about the destruction of Atlantis during the time of Ancient Greece.,_the_Lost_Continent
    The 95 min movie.

    They do not mention Archons,but the “technology” is abused just like today!
    And….at the end they blow them selves up Real Good!
    As prions are indestructible and the upper strata playing around in them in the turn of century on perhaps picked up some nice prionic parasites that destroyed the Egyptians and it took them time to reach a noticible level of presences..
    Ya never know… =-)

  4. Howie

     /  March 5, 2015

    Excerpted from “The Active Side of Infinity”

    by Carlos Castenada

    pg 217

    Don Juan said, “This is the appropriate time of day for doing what I am asking you to do. It takes a moment to engage the necessary attention to do it. Don’t stop until you catch that fleeting black shadow.”

    I did see some strange fleeting black shadow projected on the foliage of the trees. It was either a shadow going back and forth or various fleeting shadows moving side-to-side or straight up in the air. They looked like fat black fish to me, enormous fish. It was as if gigantic swordfish were flying in the air. I was engrossed in the sight. Then, finally, it scared me. It became too dark to see the foliage, yet I could still see the fleeting black shadows.

    “What is it, don Juan?” I asked.

    “[Long ago, the native sorcerer/shamans of Mexico] discovered that we have a companion for life,” he said, as clearly as he could. “We have a predator that came from the depths of the cosmos, and took over the rule of our lives. Human beings are its prisoners. The predator is our lord and master. It has rendered us docile; helpless. If we want to protest, it suppresses our protest. If we want to act independently, it demands that we don’t do so.”

    It was very dark around us, and that seemed to curtail any expression on my part. If it had been daylight, I would have laughed my head off. In the dark, I felt quite inhibited.

    “It’s pitch black around us,” don Juan said, “but if you look out of the corner of your eye, you will still see fleeting shadows jumping all around you.”

    He was right. I could still see them. Their movement made me dizzy. Don Juan turned on the light, and that seemed to dissipate everything. Don Juan said, “You have arrived, by your effort alone, to what the shamans of ancient Mexico called the topic of topics. I have been beating around the bush all this time, insinuating to you that something is holding us prisoner. Indeed we are held prisoner! This was an energetic fact for the sorcerers of ancient Mexico.”

    Why has this predator taken over in the fashion that you’re describing, don Juan?” I asked. “There must be a logical explanation.”

    “There is an explanation,” don Juan replied, “which is the simplest explanation in the world. They took over because we are food for them, and they squeeze us mercilessly because we are their sustenance. Just as we rear chickens in chicken coops, gallineros, the predators rear us in human coops, humaneros. Therefore, their food is always available to them.”

    I felt that my head was shaking violently from side to side. I could not express my profound sense of unease and discontentment, but my body moved to bring it to the surface. I shook from head to toe without any volition on my part. I heard myself saying, “No, no, no, no. This is absurd, don Juan. What you’re saying is something monstrous. It simply can’t be true, for sorcerers, or for average men, or for anyone.”

    “Why not?” don Juan asked calmly. “Why not? Because it infuriates you?”

    “Yes, it infuriates me,” I retorted. “Those claims are monstrous!”

    “Well,” he said, “you haven’t heard all the claims yet. Wait a bit longer and see how you feel. “I’m going to subject you to a blitz. That is, I’m going to subject your mind to tremendous onslaughts; and you cannot get up and leave because you’re caught. Not because I’m holding you prisoner, but because something in you will prevent you from leaving while another part of you is going to go truthfully berserk. So brace yourself!”

    There was something in me which I felt was a ‘glutton for punishment’. He was right. I wouldn’t have left the house for the world; and yet I didn’t like one bit the inanities he was spouting. Don Juan said, “I want to appeal to your analytical mind. Think for a moment, and tell me how you would explain the contradiction between the intelligence of man the engineer, and the stupidity of his systems of beliefs; or the stupidity of his contradictory behavior. Sorcerers believe that the predators have given us our systems of beliefs; our ideas of good and evil; our social mores. The predators are the ones who set up our hopes and expectations, and dreams of success or failure. They have given us covetousness, greed, and cowardice. It is the predators who make us complacent, routinary, and egomaniacal.”

    “But how can they do this, don Juan?” I asked, somehow angered further by what he was saying. “Do they whisper all that in our ears while we are asleep?”

    “No, they don’t do it that way. That’s idiotic!” don Juan said, smiling. “They are infinitely more efficient and organized than that. “In order to keep us obedient, meek and weak, the predators engaged themselves in a stupendous maneuver- stupendous, of course, from the point of view of a fighting strategist; a horrendous maneuver from the point of view of those who suffer it. They gave us their mind! Do you hear me? The predators give us their mind which becomes our mind. The predators’ mind is baroque, contradictory, morose, and filled with the fear of being discovered any minute now.

    “I know that even though you have never suffered hunger,” he went on, “you have food anxiety which is none other than the anxiety of the predator who fears that any moment now its maneuver is going to be uncovered, and its food is going to be denied. Through the mind, which after all is their mind, the predators inject into the lives of human beings whatever is convenient for them. The predators ensure in this manner a degree of security to act as a buffer against their fear.”

    “It’s not that I can’t accept all this at face value, don Juan,” I said. “I could, but there’s something so odious about it that it actually repels me. It forces me to take a contradictory stand. “If it’s true that they eat us, how do they do it?”

    Don Juan had a broad smile on his face. He was as pleased as punch. He explained that sorcerers see infant human beings as strange, luminous balls of energy covered from the top to the bottom with a glowing coat something like a plastic cover that is adjusted tightly over their cocoon of energy. He said that that glowing coat of awareness was what the predators consumed, and that when a human being reached adulthood, all that was left of that glowing coat of awareness was a narrow fringe that went from the ground to the top of the toes.That fringe permitted mankind to continue living, but only barely. As if I were in a dream, I heard don Juan explaining that, to his knowledge, man was the only species that had the glowing coat of awareness outside that luminous cocoon. Therefore, he became easy prey for an awareness of a different order; such as the heavy awareness of the predator.

    He then made the most damaging statement he had made so far. He said that this narrow fringe of awareness was the epicenter of self-reflection where man was irremediably caught. By playing on our self-reflection, which is the only point of awareness left to us, the predators create flares of awareness that they proceed to consume in a ruthless, predatory fashion. They give us inane problems that force those flares of awareness to rise, and in this manner they keep us alive in order for them to be fed with the energetic flare of our pseudo-concerns. There must have been something in what don Juan was saying which was so devastating to me that at that point I actually got sick to my stomach.

    After a moment’s pause long enough for me to recover, I asked don Juan, “But why is it that the sorcerers of ancient Mexico and all sorcerers today, although they see the predators, don’t do anything about it?”

    “There’s nothing that you and I can do about it,” don Juan said in a grave, sad voice. “All we can do is discipline ourselves to the point where they will not touch us.

    “How can you ask your fellow men to go through those rigors of discipline? They’ll laugh and make fun of you; and the more aggressive ones will beat the shit out of you… and not so much because they don’t believe it. Down in the depths of every human being, there is an ancestral, visceral knowledge about the predators’ existence.”

    My analytical mind swung back and forth like a yo-yo. It left me and came back, and left me and came back again. Whatever don Juan was proposing was preposterous, incredible. At the same time, it was a most reasonable thing; so simple. It explained every kind of human contradiction I could think of. But how could one have taken all this seriously?

    Don Juan was pushing me into the path of an avalanche that would take me down forever. I felt another wave of a threatening sensation. The wave didn’t stem from me, yet it was attached to me. Don Juan was doing something to me, mysteriously positive and terribly negative at the same time. I sensed it as an attempt to cut a thin film that seemed to be glued to me. His eyes were fixed on mine in an unblinking stare. He moved his eyes away, and began to talk without looking at me anymore.

    “Whenever doubts plague you to a dangerous point,” he said, “do something pragmatic about it. Turn off the light. Pierce the darkness; find out what you can see.” He got up to turn off the lights. I stopped him. “No, no, don Juan,” I said, “don’t turn off the lights. I’m doing okay.”

    What I felt then was a most unusual, for me, fear of the darkness. The mere thought of it made me pant. I definitely knew something viscerally, but I wouldn’t dare touch it, or bring it to the surface, not in a million years!

    “You saw the fleeting shadows against the trees,” don Juan said, sitting back against his chair. “That’s pretty good. I’d like you to see them inside this room. You’re not seeing anything. You’re just merely catching fleeting images. You have enough energy for that.”

    I feared that don Juan would get up anyway and turn off the lights, which he did. Two seconds later, I was screaming my head off. Not only did I catch a glimpse of those fleeting images, I heard them buzzing by my ears. Don Juan doubled up with laughter as he turned on the lights.

    “What a temperamental fellow!” he said. “A total disbeliever, on the one hand; and a total pragmatist on the other. You must arrange this internal fight, otherwise you’re going to swell up like a big toad and burst.”

    Don Juan kept on pushing his barb deeper and deeper into me. “The sorcerers of ancient Mexico,” he said, “saw the predator. They called it the flyer because it leaps through the air. It is not a pretty sight. It is a big shadow, impenetrably dark, a black shadow that jumps through the air. Then, it lands flat on the ground.

    “The sorcerers of ancient Mexico were quite ill at ease with the idea of when it made its appearance on Earth. They reasoned that man must have been a complete being at one point, with stupendous insights and feats of awareness that are mythological legends nowadays. And then everything seems to disappear, and we have now a sedated man.”

    I wanted to get angry and call him a paranoiac, but somehow the righteousness that was usually just underneath the surface of my being wasn’t there. Something in me was beyond the point of asking myself my favorite question: What if all that he said is true? At the moment he was talking to me that night, in my heart of hearts, I felt that all of what he was saying was true, but at the same time and with equal force, I felt that all that he was saying was absurdity itself.

    “What are you saying, don Juan?” I asked feebly. My throat was constricted. I could hardly breathe.

    “What I’m saying is that what we have against us is not a simple predator. It is very smart and organized. It follows a methodical system to render us useless. Man, the magical being that he is destined to be, is no longer magical. He’s an average piece of meat. There are no more dreams for man but the dreams of an animal who is being raised to become a piece of meat: trite, conventional, imbecilic.”

    Don Juan’s words were eliciting a strange, bodily reaction in me comparable to the sensation of nausea. It was as if I were going to get sick to my stomach again. But the nausea was coming from the bottom of my being, from the marrow of my bones. I convulsed involuntarily. Don Juan shook me by the shoulders forcefully. I felt my neck wobbling back and forth under the impact of his grip. The maneuver calmed me down at once. I felt more in control.

    “This predator,” don Juan said, “which, of course, is an inorganic being, is not altogether invisible to us as other inorganic beings are. I think as children we do see it, but we decide it’s so horrific that we don’t want to think about it. Children, of course, could insist on focusing on the sight, but everybody else around them dissuades them from doing so. The only alternative left for mankind is discipline. Discipline is the only deterrent. But by discipline I don’t mean harsh routines. I don’t mean waking up every morning at five-thirty and throwing cold water on yourself until you’re blue. Sorcerers understand discipline as the capacity to face with serenity odds that are not included in our expectations. For sorcerers, discipline is an art; the art of facing infinity without flinching; not because they are strong and tough, but because they are filled with awe.”

    “In what way would the sorcerers’ discipline be a deterrent to the flyers?” I asked.

    Don Juan scrutinized my face as if to discover any signs of my disbelief. He said,”Sorcerers say that discipline makes the glowing coat of awareness unpalatable to the flyer. The result is that the predators become bewildered. An inedible glowing coat of awareness is not part of their cognition, I suppose. After being bewildered, they don’t have any recourse other than refraining from continuing their nefarious task. If the predators don’t eat our glowing coat of awareness for a while, it will keep on growing.

    “Simplifying this matter to the extreme, I can say that sorcerers, by means of their discipline, push the predators away long enough to allow their glowing coat of awareness to grow beyond the level of the toes. Once it goes beyond the level of the toes, it grows back to its natural size. The sorcerers of ancient Mexico used to say that the glowing coat of awareness is like a tree. If it is not pruned, it grows to its natural size and volume. As awareness reaches levels higher than the toes, tremendous maneuvers of perception become a matter of course.

    “The grand trick of those sorcerers of ancient times was to burden the flyers’ mind with discipline. Sorcerers found out that if they taxed the flyers’ mind with inner silence, the foreign installation would flee, and give any one of the practitioners involved in this maneuver the total certainty of the mind’s foreign origin. The [alien mind control of these creatures] comes back, I assure you, but not as strong; and a process begins in which the fleeing of the flyers’ mind becomes routine until one day it flees permanently.

    “That’s the day when you have to rely on your own devices which are nearly zero. A sad day indeed! There’s no one to tell you what to do. There’s no mind of foreign origin to dictate the imbecilities you’re accustomed to. My teacher, the nagual Julian, used to warn all his disciples that this was the toughest day in a sorcerer’s life for the real mind that belongs to us. The sum total of our experience after a lifetime of domination has been rendered shy, insecure, and shifty. Personally, I would say that the real battle of sorcerers begins at that moment. The rest is merely preparation.”

    I became genuinely agitated. I wanted to know more, and yet a strange feeling in me clamored for me to stop. It alluded to dark results and punishment, something like the wrath of God descending on me for tampering with something veiled by God himself. I made a supreme effort to allow my curiosity to win. I heard myself say, “What-what-what do you mean, by taxing the flyers’ mind?”

    “Discipline taxes the foreign mind no end,” he replied. “So, through their discipline, sorcerers vanquish the foreign installation.”

    I was overwhelmed by his statements. I believed that don Juan was either certifiably insane or that he was telling me something so awesome that it froze everything in me. I noticed, however how quickly I rallied my energy to deny everything he had said. After an instant of panic, I began to laugh, as if don Juan had told me a joke. I even heard myself saying, “Don Juan, don Juan, you’re incorrigible!”

    Don Juan seemed to understand everything I was experiencing. He shook his head from side to side, and raised his eyes to the heavens in a gesture of mock despair. He said, “I am so incorrigible, that I am going to give the flyers’ mind which you carry inside you one more jolt. I am going to reveal to you one of the most extraordinary secrets of sorcery. I am going to describe to you a finding that took sorcerers thousands of years to verify and consolidate.”

    He looked at me, smiled maliciously, and said, “The flyers’ mind flees forever when a sorcerer succeeds in grabbing on to the vibrating force that holds us together as a conglomerate of energy fields. If a sorcerer maintains that pressure long enough, the flyers’ mind flees in defeat. And that’s exactly what you are going to do; hold on to the energy that binds you together.”

    I had the most inexplicable reaction I could have imagined. Something in me actually shook, as if it had received a jolt. I entered into a state of unwarranted fear, which I immediately associated with my religious background.

    Don Juan looked at me from head to toe. “You are fearing the wrath of God, aren’t you?” he said. “Rest assured, that’s not your fear. It’s the flyers’ fear, because it knows that you will do exactly as I’m telling you.”

    His words did not calm me at all. I felt worse. I was actually convulsing involuntarily, and I had no means to stop it.

    “Don’t worry,” don Juan said calmly. “I know for a fact that those attacks wear off very quickly. The flyer’s mind has no concentration whatsoever.”

    After a moment, everything stopped as don Juan had predicted. To say again that I was bewildered is a euphemism. This was the first time in my life ever, with don Juan or alone, that I didn’t know whether I was coming or going. I wanted to get out of the chair and walk around, but I was deathly afraid. I was filled with rational assertions, and at the same time I was filled with an infantile fear. I began to breathe deeply as a cold perspiration covered my entire body. I had somehow unleashed on myself a most godawful sight: black, fleeting shadows jumping all around me wherever I turned. I closed my eyes and rested my head on the arm of the stuffed chair.

    “I don’t know which way to turn, don Juan,” I said.

    “Tonight, you have really succeeded in getting me lost.” Don Juan said, “You’re being torn by an internal struggle. Down in the depths of you, you know that you are incapable of refusing the agreement that an indispensable part of you, your glowing coat of awareness, is going to serve as an incomprehensible source of nourishment to, naturally, incomprehensible entities.

    “And another part of you will stand against this situation with all its might. The sorcerers’ revolution is that they refuse to honor agreements in which they did not participate. Nobody ever asked me if I would consent to being eaten by beings of a different kind of awareness. My parents just brought me into this world to be food, like themselves, and that’s the end of the story.”

    Don Juan stood up from his chair and stretched his arms and legs. “We have been sitting here for hours. It’s time to go into the house. I’m going to eat. Do you want to eat with me?”

    I declined. My stomach was in an uproar.

    “I think you’d better go to sleep,” he said. “The blitz has devastated you.”

    I didn’t need any further coaxing. I collapsed onto my bed, and fell asleep like the dead.

    [When I arrived] home, as time went by, the idea of the flyers became one of the main fixations of my life. I got to the point where I felt that don Juan was absolutely right about them. No matter how hard I tried, I couldn’t discard his logic. The more I thought about it, and the more I talked to and observed myself, and my fellow men, the more intense the conviction that something was rendering us incapable of any activity or any interaction or any thought that didn’t have the self as its focal point.

    My concern, as well as the concern of everyone I knew or talked to, was the self. Since I couldn’t find any explanation for such universal homogeneity, I believed that don Juan’s line of thought was the most appropriate way of elucidating the phenomenon. I went as deeply as I could into readings about myths and legends. In reading, I experienced something I had never felt before: Each of the books I read was an interpretation of myths and legends. In each one of those books, a homogeneous mind was palpable. The styles differed, but the drive behind the words was homogeneously the same: Even though the theme was something as abstract as myths and legends, the authors always managed to insert statements about themselves.

    The homogeneous drive behind every one of those books was not the stated theme of the book. Instead, it was self-service. I had never felt this before. I attributed my reaction to don Juan’s influence. The unavoidable question that I posed to myself was: Is he influencing me to see this, or is there really a foreign mind dictating everything we do? I lapsed, perforce, into denial again, and I went insanely from denial to acceptance to denial. Something in me knew that whatever don Juan was driving at was an energetic fact; but something equally important in me knew that all of that was guff.

    The end result of my internal struggle was a sense of foreboding; the sense of something imminently dangerous coming at me. I made extensive anthropological inquiries into the subject of the flyers in other cultures, but I couldn’t find any references to them anywhere. Don Juan seemed to be the only source of information about this matter.

    The next time I saw him, I instantly jumped to talk about the flyers. I said, “I have tried my best to be rational about this subject matter, but I can’t. There are moments when I fully agree with you about the predators.”

    “Focus your attention on the fleeting shadows that you actually see,” don Juan said with a smile. I told don Juan that those fleeting shadows were going to be the end of my rational life. I saw them everywhere. Since I had left his house, I was incapable of going to sleep in the dark. To sleep with the lights on did not bother me at all. The moment I turned the lights off, however, everything around me began to jump. I never saw complete figures or shapes. All I saw were fleeting black shadows.

    “The flyers’ mind has not left you,” don Juan said. “It has been seriously injured. It’s trying its best to rearrange its relationship with you. But something in you is severed forever. The flyer knows that. The real danger is that the flyers’ mind may win by getting you tired and forcing you to quit by playing the contradiction between what it says and what I say.

    “You see, the flyers’ mind has no competitors. When it proposes something, it agrees with its own proposition, and it makes you believe that you’ve done something of worth. The flyers’ mind will say to you that whatever Juan Matus is telling you is pure nonsense, and then the same mind will agree with its own proposition, ‘Yes, of course, it is nonsense,’ you will say. That’s the way they overcome us.

    “The flyers are an essential part of the universe, and they must be taken as what they really are; awesome, monstrous. They are the means by which the universe tests us. We are energetic probes created by the universe,” he continued as if he were oblivious to my presence, “and it’s because we are possessors of energy that has awareness that we are the means by which the universe becomes aware of itself.

    “The flyers are the implacable challengers. They cannot be taken as anything else. If we succeed in doing that, the universe allows us to continue.”

  5. Reblogged this on deinvestiture.

  1. My Life: The End Of A Journey | REALITY BLOG

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