prions

So You’re Going to Eat a Brain…

The human brain is an extremely nutrient-dense food, but not an easy one to plan a balanced diet around. Let’s say you have a smallish but healthy adult male. Their brain is probably around 1300 cubic centimeters (and with its density, its volume is directly proportional to its weight of 1300 grams).

Like most of the body, the brain is primarily water. In a healthy adult, it’s about 77% H2O.

Of the remaining 23%, the nutrient breakdown is as follows:

11% fat = 143 gm fat - 143gm * 9 Cal/gm = 1287 Cal

8% protein = 104 gm protein - 104 * 4 Cal/gm = 416 Cal

1% carbohydrate = 13 gm carbohydrates - 13 * 4 = 52 Cal

In total, a human brain contains between 1700 and 2100 calories, depending upon if the dura mater is consumed (dura not included in above calculations).

Because of the density of neurons in the human brain, we have a lower percentage of our brain dedicated to myelination, which is extremely cholesterol-rich.

However, while we have a lower percentage of cholesterol per volume than beef or pork brain, it’s still extremely high. One human brain would yield approximately 38,000 mg of cholesterol, or about 12,600% your recommended daily intake.

The brain is also a source of incurable diseases caused by prions, known as the transmissible spongiform encephalopathies. Prions are extremely heat-resistant so even if you cook your brains, that’s no guarantee that you won’t contract a condition such as Creutzfeldt–Jakob disease or kuru.

These conditions are extremely rare, however, so I’d be more concerned about your cholesterol intake (and maybe the fact that you’re eating a human brain), first.

Image:
Traité de phrénologie humaine et comparée. Joseph Vimont, 1832-1835.

Brain Facts and Figures

A prion, pictured above, is an infectious agent comprised only of a protein in misfolded form. It lies in stark contrast to all other known infectious agents; even the simplest bacterium or virus contains nucleic acids (either DNA, RNA, or both) but amazingly, prions seem to have neither. Instead, they propagate by transmitting a misfolded protein state - meaning that when a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, prion form. The prion essentially acts as a template to guide the misfolding of more cellular proteins; newly formed prions can then go on to convert more other proteins, triggering a chain reaction that produces the prion form in exponentially large numbers.

Prions are responsible for the transmissible spongiform encephalopathies in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as “mad cow disease”) in cattle and Creutzfeldt–Jakob disease (CJD) in humans. All known prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and universally fatal.

Randomly getting on the topic of cannibalism in class
  • Random girl:Yeah so like if a person eats human flesh they get these crazy trembles and stuff and die
  • Random guy:yeah and it's like rabies
  • Me:Actually, it's only when you eat the brain, and the brain is infected with prions, which cause the neurodegenerative disorders that you attribute the "shaking" and "rabid" behavior to.
  • Class:...
  • Professor:...
  • Professor:...how do you know this?
  • Me:Writer.

What Makes Memories Last?

Prions can be notoriously destructive, spurring proteins to misfold and interfere with cellular function as they spread without control. New research, published in the open access journal PLOS Biology on February 11, 2014, from scientists at the Stowers Institute for Medical Research reveals that certain prion-like proteins, however, can be precisely controlled so that they are generated only in a specific time and place. These prion-like proteins are not involved in disease processes; rather, they are essential for creating and maintaining long-term memories.

“This protein is not toxic; it’s important for memory to persist,” says Stowers researcher Kausik Si, Ph.D., who led the study. To ensure that long-lasting memories are created only in the appropriate neural circuits, Si explains, the protein must be tightly regulated so that it adopts its prion-like form only in response to specific stimuli. He and his colleagues report on the biochemical changes that make that precision possible.

Si’s lab is focused on finding the molecular alterations that encode a memory in specific neurons as it endures for the days, months, or years—even as the cells’ proteins are degraded and renewed. Increasingly, their research is pointing toward prion-like proteins as critical regulators of long-term memory.

In 2012, Si’s group demonstrated that prion formation in nerve cells is essential for the persistence of long-term memory in fruit flies. Prions are a fitting candidate for this job because their conversion is self-sustaining: once a prion-forming protein has shifted into its prion shape, additional proteins continue to convert without any additional stimulus.

Si’s team found that in fruit flies, the prion-forming protein Orb2 is necessary for memories to persist. Flies that produce a mutated version of Orb2 that is unable to form prions learn new behaviors, but their memories are short-lived. “Beyond a day, the memories become unstable. By three days, the memory has completely disappeared,” Si explains.

In the new study, Si wanted to find out how this process could be controlled so that memories form at the right time. “We know that all experiences do not form long-term memory—somehow the nervous system has a way to discriminate. So if prion-formation is the biochemical basis of memory, it must be regulated.” Si says. “But prion formation appears to be random for all the cases we know of so far.”

Si and his colleagues knew that Orb2 existed in two forms—Orb2A and Orb2B. Orb2B is widespread throughout the fruit fly’s nervous system, but Orb2A appears only in a few neurons, at extremely low concentrations. What’s more, once it is produced, Orb2A quickly falls apart; the protein has a half-life of only about an hour.

“When Orb2A binds to the more abundant form, it triggers conversion to the prion state, acting as a seed for the conversion. Once conversion begins, it is a self-sustaining process; additional Orb2 continues to convert to the prion state, with or without Orb2A. By altering the abundance of the Orb2A seed”, Si says, “cells might regulate where, when, and how the conversion process is engaged”. But how do nerve cells control the abundance of the Orb2A seed?

Their experiments revealed that when a protein called TOB associates with Orb2A , it becomes much more stable, with a new half-life of 24 hours. This step increases the prevalence of the prion-like state and explains how Orb2’s conversion to the prion state can be confined in both time and space.

The findings raise a host of new questions for Si, who now wants to understand what happens when Orb2 enters its prion-like state, as well as where in the brain the process occurs. While unraveling these mechanisms will likely be more accessible in the fruit fly than in more complex organisms, Si points out that proteins related to Orb2 and TOB have also been found in the brains of mice and humans. He has already shown that in the sea snail Aplysia, conversion to a prion-like state facilitates long-term change in synaptic strength. “This basic mechanism appears to be conserved across species,” he notes.

Genetic mutation blocks prion disease

Scientists who study a rare brain disease that once devastated entire communities in Papua New Guinea have described a genetic variant that appears to stop misfolded proteins known as prions from propagating in the brain.

Kuru was first observed in the mid-twentieth century among the Fore people of Papua New Guinea. At its peak in the late 1950s, the disease killed up to 2% of the group’s population each year. Scientists later traced the illness to ritual cannibalism, in which tribe members ate the brains and nervous systems of their dead. The outbreak probably began when a Fore person consumed body parts from someone who had sporadic Creutzfeldt-Jakob disease (CJD), a prion disease that spontaneously strikes about one person in a million each year.

Scientists have noted previously that some people seem less susceptible to prion diseases if they have an amino-acid substitution in a particular region of the prion protein — codon 129. And in 2009, a team led by John Collinge — a prion researcher at University College London who is also the lead author of the most recent analysis — found another protective mutation among the Fore, in codon 127.

The group’s latest work, this month in Nature, shows that the amino-acid change that occurs at this codon, replacing a glycine with a valine, has a different and more powerful effect than the substitution at codon 129. The codon 129 variant confers some protection against prion disease only when it is present on one of the two copies of the gene that encodes the protein. But transgenic mice with the codon-127 mutation were completely resistant to kuru and CJD regardless of whether they bore one or two copies of it.

The researchers say that the mutation in codon 127 appears to confer protection by preventing prion proteins from becoming misshapen.

“It is a surprise,” says Eric Minikel, a prion researcher at the Broad Institute in Cambridge, Massachusetts. “This was a story I didn’t expect to have another chapter.”

Collinge and his colleagues are now continuing their work, to figure out the mutant protein’s structure and how it shields against illness.

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nature.com
Genetic mutation blocks prion disease
Unknown mechanism helped some people in Papua New Guinea escape historic, deadly outbreak.

Scientists who study a rare brain disease that once devastated entire communities in Papua New Guinea have described a genetic variant that appears to stop misfolded proteins known as prions from propagating in the brain1.

Kuru was first observed in the mid-twentieth century among the Fore people of Papua New Guinea. At its peak in the late 1950s, the disease killed up to 2% of the group’s population each year. Scientists later traced the illness to ritual cannibalism2, in which tribe members ate the brains and nervous systems of their dead. The outbreak probably began when a Fore person consumed body parts from someone who had sporadic Creutzfeldt-Jakob disease (CJD), a prion disease that spontaneously strikes about one person in a million each year.

Scientists have noted previously that some people seem less susceptible to prion diseases if they have an amino-acid substitution in a particular region of the prion protein — codon 1293. And in 2009, a team led by John Collinge — a prion researcher at University College London who is also the lead author of the most recent analysis — found another protective mutation among the Fore, in codon 1274.

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The Bright Side of Prions

Associated with numerous neurological diseases, misfolded proteins may also play decisive roles in normal cellular functioning.

In Kurt Vonnegut’s Cat’s Cradle, scientists create a highly stable form of crystalline water called “ice-nine” that stays frozen even at high temperatures. Ice-nine instantly freezes any liquid water it touches. Its accidental release into nature solidifies the oceans and all contiguous bodies of water, and global catastrophe threatens our existence. Luckily for us, ice-nine is fictitious. But its biological counterpart, unfortunately, is not. The misfolded proteins known as prions are very real.

Prions are proteinaceous infectious particles, formed when normal proteins misfold and clump together. Biochemists Byron Caughey of the National Institute of Allergy and Infectious Diseases and Peter Lansbury of Brigham and Women’s Hospital were among the first to explore the analogy between Vonnegut’s ice-nine and prions in their 1995 review of scrapie, an infectious and deadly neurological disease of sheep. Like ice-nine, the particles that spread scrapie consist of highly stable crystals of a normally innocuous material found in the brains of sheep. Crystalline clumps of a misfolded version of this protein coax other molecules of the same protein to fold into the aberrant conformation. The process continues until virtually all of that protein in a cell or tissue has been converted to prions. In the case of scrapie and other mammalian prion diseases, the consequence of this self-amplifying cycle is an accumulation of toxic clumps of proteins that destroys neurons and invariably kills the organism.

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Scholarly Resource Alert! David Grove, author of Tapeworms, Lice, and Prions: A compendium of unpleasant infections, alerted us to a BBC series, starting Wednesday 19 February, in which Dr Michael Mosley turns his body into a living laboratory by deliberately infecting himself with some extraordinary parasites. (via BBC - Media Centre - Programme Information - Michael Mosley: Infested! Living With Parasites)

(Image caption: Given an opportunity to spread in cells, prion-like proteins taken from the brains of patients with (from top) Alzheimer’s disease, corticobasal degeneration and Pick’s disease form distinctly shaped clumps (green in this image) in different parts of the cells. Credit: David W. Sanders)

Alzheimer’s disease, other conditions linked to prion-like proteins

A new theory about disorders that attack the brain and spinal column has received a significant boost from scientists at Washington University School of Medicine in St. Louis.

The theory attributes these disorders to proteins that act like prions, which are copies of a normal protein that have been corrupted in ways that cause diseases. Scientists previously thought that only one particular protein could be corrupted in this fashion, but researchers in the laboratory of Marc Diamond, MD, report that another protein linked to Alzheimer’s disease and many other neurodegenerative conditions also behaves very much like a prion.

The findings appear online May 22 in Neuron.

Diamond’s lab found that the protein, known as tau, could be corrupted in different ways, and that these different forms of corruption — known as strains — were linked to distinct forms of damage to the brain.

“If we think of these different tau strains as different pathogens, then we can begin to describe many human disorders linked to tau based on the strains that underlie them,” said senior author Diamond, the David Clayson Professor of Neurology. “This may mean that certain antibodies or drugs, for example, will work better against certain disorders than others.”

The study was led by co-first authors David Sanders and Sarah Kaufman, who are graduate students.

Prions are composed of normal proteins that have folded into an abnormal shape. They aren’t alive, but their effects can be similar to infectious microbes such as bacteria or viruses. Their unusual structure lets prions replicate themselves through a kind of molecular peer pressure: When a prion interacts with identical but normally folded proteins, it can cause these proteins to become prions, which are small aggregates, or clumps, that can spread from cell to cell.

Prions first came to popular attention in the 1990s with the emergence of mad cow disease, a disorder that destroys the brains of cattle. Scientists linked a few cases of a similar condition in people to consumption of meat from infected cows. Researchers eventually determined that the disorder was caused by a distinct strain of prions made by the sickened cattle.

Scientists had suspected that prion-like forms of a protein called alpha-synuclein contribute to Parkinson’s disease and other conditions, and prion-like versions of proteins known as SOD1 and TDP43 may cause amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease.

Scientists also had identified tau clumps in 25 different neurodegenerative disorders, known collectively as tauopathies. This hinted at potential prion-like behavior on the part of tau. In 2009, Diamond’s group found that tau misfolds into several different shapes in a test tube.

“When we infected a cell with one of these misshapen copies of tau and allowed the cell to reproduce, the daughter cells contained copies of tau misfolded in the same fashion as the parent cell,” Diamond said. “Further, if we extracted the tau from an affected cell, we could reintroduce it to a naïve cell, where it would recreate the same aggregate shape. This proves that each of these differently shaped copies of the tau protein can form stable prion strains, like a virus or a bacteria, that can be passed on indefinitely.”

Diamond used the tau prions made in cells to infect mouse brains, showing that differently shaped strains caused different levels of brain damage. He isolated the prions from the mice, grew them in cell culture, and then infected other mice. Throughout these transfers, each particular prion strain continued to be misfolded in the same shape and to cause damage in the same fashion.

Finally, the researchers examined clumps of tau from the brains of 28 patients after they died. Each of the patients was known to have one of five forms of tauopathy.

“Each disease had a unique tau prion strain or combination of strains associated with it,” he said. “For example, we isolated the same tau prion strain from nearly every patient with Alzheimer’s disease we examined.”

Brain samples from patients with the progressive neurological disorderscorticobasal degeneration and Pick’s disease also typically had the same tau prion strains or mixtures of strains.

Diamond and others now are working to find a way to isolate tau prions non-invasively from individuals for diagnostic purposes.

Options for stopping prions include monoclonal antibodies, which could label prions for inactivation or immune system attack and removal (described in a paper by Diamond and David Holtzman, MD, Chair of Neurology (Neuron, 2013)). Diamond and others also are developing ways to block tau prion movement between cells and to stop cells from making new copies of the prion proteins.

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Mad Cow Research Hints At Ways To Halt Alzheimer’s, Parkinson’s

Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis ravage the brain in very different ways. But they have at least one thing in common, says Corinne Lasmezas, a neuroscientist and professor at Scripps Research Institute, in Jupiter, Fla. Each spreads from brain cell to brain cell like an infection.

“So if we could block this [process], that might prevent the diseases,” Lasmezas says.

It’s an idea that’s being embraced by a growing number of researchers these days, including Nobel laureate Dr. Stanley Prusiner, who first recognized in the 1980s the infectious nature of brain proteins that came to be called prions. But the idea that mad cow prions could cause disease in people has its origins in an epidemic of mad cow disease that occurred in Europe and the U.K. some 15 years ago.

Back then, Lasmezas was a young researcher in France studying how mad cow, formally known as bovine spongiform encephalopathy, was transmitted. “At that time, nobody knew if this new disease in cows was actually transmissible to humans,” she says.

In 1996, Lasmezas published a study strongly suggesting that it was. “So that was my first great research discovery,” she says.

In 2005, Lasmezas came to Scripps Florida, where she continued to study the toxic particles responsible for mad cow and its human equivalent.

Prions, it turns out, become toxic to brain cells when folded into an abnormal shape. “This misfolded protein basically kills the neurons,” Lasmezas says.

Neurons, like other cells, depend on proteins to carry out essential tasks, like defending against germs and regulating metabolism. But to function correctly, a protein must be folded into exactly the right shape. If it folds into the wrong shape, it can kill a cell.

As scientists learned more about prion diseases like mad cow, they began to realize that misfolded proteins had a role in several human brain diseases. “Little by little,” Lasmezas says, “it became clear that there are a lot of common features between prion diseases and the other diseases like Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis.”

In Alzheimer’s, proteins called beta-amyloid and tau misfold and form clumps. That leads to the distinctive plaques and tangles that build up in a patient’s brain. In Parkinson’s and ALS, different proteins misfold and aggregate.

In prion diseases like mad cow, the misfolded proteins spread by somehow causing normal, adjacent proteins to change shape. So a few years ago, researchers looked to see whether the abnormal proteins spread from neuron to neuron the same way in other brain diseases.

The evidence was clear, Lasmezas says. “These aggregated proteins are not only transmissible from cell to cell in prion diseases, they are also transmissible cell to cell in Alzheimer’s disease, in Parkinson’s disease, in ALS.”

When these misfolded proteins reach a critical mass, they appear to start a chain reaction that eventually destroys the brain. So Lasmezas and many other researchers are looking for ways to slow or halt that chain reaction.

One approach is to find drugs that can neutralize misfolded proteins before they spread. Another is to protect brain cells from the damage usually caused by a misfolded protein. Lasmezas and her colleague Minghai Zhou are part of a team that describe a way to do this in the current issue of the journal Brain.

The experiment involved a prion protein that kills neurons by depleting their supply of a molecule called NAD.

“What we found is that if you replenish NAD in these neurons, it completely protects them against the injury caused by misfolded prion protein,” Lasmezas says.

That suggests the right drugs could protect brain cells from the misfolded proteins involved in Alzheimer’s and Parkinson’s and ALS, Lasmezas says.

But protecting cells is an approach designed to slow down brain diseases, not stop them. To stop the problem, she says, researchers will have to figure out precisely how normal proteins become corrupted. “We need to understand how they change their shape. What makes them misfold? What happens to them?”

The research on misfolded proteins is changing how scientists view diseases like Alzheimer’s and Parkinson’s, says Margaret Sutherland, a program director at the National Institute of Neurological Disorders and Stroke, which funds Lasmezas’ research. “It’s opened up a different mechanism for understanding the pathology behind neurodegenerative diseases,” she says.

But there’s still no way of knowing, she adds, whether this new understanding will lead to new treatments for these diseases.

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Eating Human Brains Drove Evolution In Remote Tribe

The practice of ritualistic mortuary cannibalism used to be common amongst the Fore peoples of Papua New Guinea. When a member of the tribe died, the women in the village used to dismember and prepare the body, which was then eaten. They would often feed bits of the brain to the children and elderly.

It was this custom of eating the brain of the deceased that is thought to have caused the epidemic in the 1950s of “human mad cow disease,” known as kuru, within the Fore peoples. Now, scientists have identified a genetic mutation that likely helped to protect the Fore against developing the illness, a type of prion disease caused by misfolded proteins. This specific mutation was also shown to protect against all other forms of prion disease, such as Creutzfeldt-Jakob disease (CJD).

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Prions: The Real Zombie-Makers

Hank is tired of zombies in popular culture, and while acknowledging that dead people are scary (especially if they start moving around), he brings us some information on prions - misfolded proteins that are responsible for destroying brains and get passed around mostly by getting eaten. So yeah, zombie stuff.

Small Loop in Human Prion Protein Prevents Chronic Wasting Disease
Finding provides new therapeutic target for prion diseases

Chronic wasting disease (CWD) — an infectious disease caused by prions — affects North American elk and deer, but has not been observed in humans. Using a mouse model that expresses an altered form of the normal human prion protein, researchers at University of California, San Diego School of Medicine have determined why the human proteins aren’t corrupted when exposed to the elk prions. Their study, published Feb. 23 in the Journal of Clinical Investigation, identifies a small loop in the human prion protein that confers resistance to chronic wasting disease.

“Since the loop has been found to be a key segment in prion protein aggregation, this site could be targeted for the development of new therapeutics designed to block prion conversion,” said Christina Sigurdson, DVM, PhD, associate professor at UC San Diego and UC Davis and senior author of the study.

Prions aren’t microorganisms like bacteria or viruses; they’re simply protein aggregates. Some prion diseases are caused by an inherited genetic mutation, while others are caused by exposure to infectious prions in food. Acquired prion diseases are triggered when a foreign, misfolded prion protein causes the body’s own natural prion proteins to misfold and aggregate. In addition to chronic wasting disease, examples include scrapie and bovine spongiform encephalopathy (or “mad cow disease”) in animals and variant Creutzfeldt-Jakob disease in humans. In humans, prion diseases can cause a variety of rapidly progressive neurological symptoms, such as difficulty walking and speaking, and dementia. These diseases are 100 percent fatal and there is currently no effective treatment.

“We suspected that a loop in the human prion protein structure may block the elk prions from binding, as the sequences did not appear to be compatible,” Sigurdson said.

To test this hypothesis, Sigurdson and her team developed a transgenic mouse that expresses a prion protein that’s identical to the human version — except for a small loop, which they swapped out for the elk prion sequence. When these mice were exposed to the elk prions, they developed chronic wasting disease.

In contrast, control mice expressing the normal human prion sequence resisted infection when exposed to same materials — just as humans seem to, even those who consume venison meat.

“This finding suggests that the loop structure is crucial to prion conversion and that sequence compatibility with the host prion protein at this site is required for the transmission of certain prion diseases,” Sigurdson said.  

Pictured: Prion protein aggregates (brown) in the brain of a mouse expressing the human-elk protein. UC San Diego School of Medicine

Scientists Identify First Potentially Effective Therapy for Human Prion Disease

Human diseases caused by misfolded proteins known as prions are some of most rare yet terrifying on the planet—incurable with disturbing symptoms that include dementia, personality shifts, hallucinations and coordination problems. The most well-known of these is Creutzfeldt-Jakob disease, which can be described as the naturally occurring human equivalent of mad cow disease.

Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time identified a pair of drugs already approved for human use that show anti-prion activity and, for one of them, great promise in treating these universally fatal disorders.

The study, led by TSRI Professor Corinne Lasmézas and performed in collaboration with TSRI Professor Emeritus Charles Weissmann and Director of Lead Identification Peter Hodder, was published this week online ahead of print by the journal Proceedings of the National Academy of Sciences.

The new study used an innovative high-throughput screening technique to uncover compounds that decrease the amount of the normal form of the prion protein (PrP, which becomes distorted by the disease) at the cell surface. The scientists found two compounds that reduced PrP on cell surfaces by approximately 70 percent in the screening and follow up tests.

The two compounds are already marketed as the drugs tacrolimus and astemizole.

Tacrolimus is an immune suppressant widely used in organ transplantation. Tacrolimus could prove problematic as an anti-prion drug, however, because of issues including possible neurotoxicity.

However, astemizole is an antihistamine that has potential for use as an anti-prion drug. While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in more than 30 countries and has a well-established safety profile. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration.

Lasmézas noted that astemizole appears to stimulate autophagy, the process by which cells eliminate unwanted components. “Autophagy is involved in several protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases,” she said. “So future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders.”

The study noted that eliminating cell surface PrP expression could also be a potentially new approach to treat Alzheimer’s disease, which is characterized by the build-up of amyloid β plaque in the brain. PrP is a cell surface receptor for Aβ peptides and helps mediate a number of critical deleterious processes in animal models of the disease.

Scrapie fibrils. Coloured transmission electron micrograph of fibrils associated with scrapie. This is a form of transmissible, slow virus encephalopathy which affects sheep & goats. Human slow virus encephalopathies include Kuru, Creutzfeldt-Jakob disease, & Gerstmann-Straussler syndrome. The agents causing these diseases form a group of virus-like organisms called prions. Prions are small protein-particles which appear to be self- replicating but uniquely contain no nucleic acid. Scrapie-associated fibrils are believed to be aggregations of the major proteins of the infectious agents. Magnification:x58,000 at 6x6cm size. x200,000 at 8x10 inch size.

Eating brains helped Papua New Guinea tribe resist disease

Research involving a former brain-eating tribe from Papua New Guinea is helping scientists better understand mad cow disease and other so-called prion conditions and may also offer insights into Parkinson’s and dementia.

People of the Fore tribe, studied by scientists from Britain and Papua New Guinea, have developed genetic resistance to a mad cow-like disease called kuru, which was spread mostly by the now abandoned ritual of eating relatives’ brains at funerals.

Experts say the cannibalistic practice led to a major epidemic of kuru prion disease among the Fore people, which at its height in the late 1950s caused the death of up to 2% of the population each year.

In findings published in the scientific journal Nature, the researchers said they had identified the specific prion resistance gene – and found that it also protects against all other forms of Creutzfeldt-Jakob disease (CJD).

“This is a striking example of Darwinian evolution in humans, the epidemic of prion disease selecting a single genetic change that provided complete protection against an invariably fatal dementia,” said John Collinge of the Institute of Neurology’s prion unit at University College London, which co-led the work.

Papua New Guinea Photograph: Lloyd Jones/AAP Image

Alzheimer’s Disease and Other Conditions Linked to Prion-Like Proteins

A new theory about disorders that attack the brain and spinal column has received a significant boost from scientists at Washington University School of Medicine in St. Louis.

The theory attributes these disorders to proteins that act like prions, which are copies of a normal protein that have been corrupted in ways that cause diseases. Scientists previously thought that only one particular protein could be corrupted in this fashion, but researchers in the laboratory of Marc Diamond, MD, report that another protein linked to Alzheimer’s disease and many other neurodegenerative conditions also behaves very much like a prion.

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The good side of the prion: A molecule that is not only dangerous, but can help the brain grow

A few years ago it was found that certain proteins, the prions, when defective are dangerous, as they are involved in neurodegenerative syndromes such as the Creutzfeldt-Jakob and the Alzheimer diseases. But now research is showing their good side, too: when performing well, prions may be crucial in the development of the brain during childhood, as observed by a study carried out by a team of neuroscientists at Trieste’s SISSA which appeared yesterday in the Journal of Neuroscience.

Doctor Jekyll and Mr. Hyde: the metaphor of the good man who hides an evil side suits well the prion (PrPC in its physiological cellular form), a protein which abounds in our brain. Unlike Doctor Jekyll, the prion was at first considered for its upsetting properties: if the molecule abnormally folds over itself it unfortunately plays a crucial role in neurodegenerative processes that lead to dreadful syndromes such as the mad cow disease.

Prions, however, in their normal form abound in synapses, the contact points where the nervous signal is passed from a neuron to the next. Such protein relatively abounds in the brain of very young children, and this is the reason why scientists have assumed it may play a role in the
nervous system development, and in particular in neurogenesis, in the development of new synaptic connections and in plasticity.

More in detail

Maddalena Caiati, Victoria Safiulina, Sudhir Sivakumaran, Giuseppe Legname, Enrico Cherubini, all researchers at SISSA, and Giorgia Fattorini of the Università Politecnica delle Marche have verified at the molecular level the effects of PrPC on the cell plasticity of the hippocampus, a brain structure which has important functions related to memory. Maddalena Caiati and her colleagues have demonstrated that PrPC controls synaptic plasticity (the growth capacity of the nervous tissue) through a transduction pathway which involves also another protein, the protein kinase A enzyme (PKA). The recently published research is only the starting point. As for the future, it will be interesting to get a closer look at the role played by the prion protein in the development of neuronal circuits both under physiological and pathologic conditions in neurodegenerative diseases.