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When does oxidation destroy prions?

When does oxidation destroy prions?



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It seems like a no-brainer than oxidation, playing the, er, role it does in the universe, would destroy prions just like it destroys everything else.

But when does it do that? I assume this has been studied, since people handle them in laboratories and may need to sterilize their instruments.


Prions are fairly resistant to traditional method of sterilization.

Citing from: Guideline for Disinfection and Sterilization of Prion-Contaminated Medical Instruments

The prions that cause CJD and other TSEs exhibit an unusual resistance to conventional chemical and physical decontamination methods. Because the CJD agent is not readily inactivated by means of conventional disinfection and sterilization procedures and because of the invariably fatal outcome of CJD, the procedures for disinfection and sterilization of the CJD prion have been both cautious and controversial for many years.

The same paper also lists several effective and ineffective methods for sterilization (efficient method have > 3log10 reduction in prion content within 1 hour) I am not going to list them all here but you can see Table 2 in the paper.

Just to answer your specific question about oxydation, certain oxydising agents are effective, others are not. Similarly certain autoclaving (=sterilising with heat) procedures are fine and others are not.

Another interesting paper Methods to Minimize the Risks of Creutzfeldt-Jakob Disease Transmission by Surgical Procedures: Where to Set the Standard?


If you google "prion oxidation" you'll see that there has been some research into this over the last 10 years, though it seems to be a minor focus of the overall field. There seems to be some interest currently in using ozone to inactivate prions. One company that offers a ozone-based sterilizer claims to be testing for effectiveness against prions, but that is an extremely long-term process (you have to isolate prions, subject them to your sterilization process, then inject them into the brains of mice or hamsters and wait to see if disease develops).

If you're curious as to how researchers sterilize material in the lab, I may be able to shed some light on that (I worked in a prion lab in 2006-07). Generally, disposable instruments and materials are used whenever possible and incinerated after use. Glassware is submerged in acidic detergent and autoclaved for 4 hours at (I believe) 132C. As far as I know, there is still no known way to completely sterilize stainless steel instruments - this was being studied at the time in the lab where I worked. Any piece of equipment that came in contact with human or bovine prions was kept in Biosafety Level 3 facilities permanently. I'm not sure what the decontamination process was for retired equipment. Separate equipment was maintained for "non-human pathogen" prions - hamster, mouse, etc.


Killing prions with ozone

When it comes to infectious agents, it doesn’t get much worse than prions. These misfolded proteins are highly resistant to a wide variety of extreme disinfectant procedures. They have been identified as the culprits behind mad cow disease and chronic wasting disease in animals and humans, and are also implicated in Creutzfeldt-Jakob disease and other prion-related disorders.

But an interdisciplinary University of Alberta research team has come a step closer to finding a way of inactivating these highly infectious proteins.

The team, lead by environmental health professors Mike Belosevic and Norm Neumann from the School of Public Health and engineering professor Mohamed Gamal El-Din from the Department of Civil and Environmental Engineering, have demonstrated for the first time that prions are highly susceptible to molecular ozone.

The discovery could have implications for decontaminating medical and dental surgical instruments or treating water and wastewater in settings where prions might appear, such as in slaughterhouse waste.

“Although we know that they have a very high-level resistance, it’s possible that we’ve discovered their Achilles’ heel,” said Neumann. “This means there might be simple solutions to dealing with contaminated medical instruments and waste products from slaughterhouses.”

Human transmission of these devastating infectious agents through patient exposure to surgical equipment and blood transfusions has been documented. If these proteins can be neutralized, the result will be improved patient care.

“Because ozone is already commonly used in the hospital environment, the technology for this disinfection process already exists,” says Neumann. “It is possible to take a medical instrument, put it in an ozone bath and very quickly destroy 99.99% of the prions that are there.”

However, there is still much work to do. “The only proof of final inactivation is to actually infect animals, and it may take years for the animal to start demonstrating the behavioural changes associated with these diseases caused by prions,” says Neumann. “We need more research in this area to increase our understanding of the relationship between ozone and all types of prions, including bovine spongiform encephalopathy or BSE, and that’s what we’re working on now.”

The interdisciplinary nature of the research proved to be crucial to the success. “Nobody has really taken the biological diagnostics and methods and then applied them in the engineering context, and that’s what we did here,” Neumann said.

The importance of the interdisciplinary approach to this research is echoed by Gamal El-Din. “We have the expertise in microbiology and engineering to make a difference. The ultimate goal is to protect the health of people as well as the environment.”

The research was funded in part by the Alberta Prion Research Institute, PrioNet Canada and the Natural Sciences and Engineering Research Council of Canada and published in the February issue of the journal Applied and Environmental Microbiology.


In 1996, the British government announced that ten suspected cases of Creutzfeld-Jacob disease (CJD), a degenerative brain disorder, were caused by the consumption of beef products that harbor mad cow disease [1]. This news not only prompted the EU and Japan to institute a ban on British beef products, but also redirected the attention of the scientific community to the bizarre infectious agent responsible for causing these similar and devastating diseases (mad cow disease in cattle and CJD in humans). This infectious agent, called the prion, is responsible for causing a group of fatal neurodegenerative diseases in mammals referred to as transmissible spongiform encephalopathies (TSEs) [2]. In these diseases, prions cause holes to form in the brains of the affected individuals, giving the brain a sponge-like appearance, hence the term spongiform. Affected individuals develop progressively worsening dementia and eventually die. Another example of a prion disease in humans is the Kuru disease in Papua New Guinea, which spreads among tribal people when they eat the brains of deceased relatives during funeral rituals. Prions cause fatal diseases in sheep as well, such as sheep scrapie, and it is believed that sheep may have transmitted the first prions to cows.

The discovery of an infectious protein

Scientists have been trying to identify the cause of these fatal “sponge-like” brain diseases since 1967 but had limited success. Whatever was causing these diseases was infectious, and could spread from human to human, like in Kuru disease, but also between different species (e.g. cows to humans). Scientists initially thought of the usual suspects, namely viruses and bacteria, as these agents are known to spread among individuals and, in some cases, between species. However, scientists could not kill this infectious agent the way one would kill viruses or bacteria. For instance, heat and UV radiation kill viruses and bacteria by destroying their genetic material, which is crucial to their existence. However, this mysterious infectious agent was resistant to heat and UV radiation and continued to spread as if nothing had happened to it, strongly suggesting that it was neither a virus nor a bacterium. This is why infected beef is still not safe to eat even after cooking it at very high temperatures.

A breakthrough came in 1982, when Stanley Prusiner from the University of California, San Francisco found that the infectious agent causing TSEs was actually a single protein. He called this protein “prion”, which means infectious protein. His discovery was initially met with great skepticism among the scientific community, as most scientists did not believe that proteins could be infectious. Despite all the criticisms, Prusiner went on to discover that the prion protein is native to many mammals, including humans, meaning that we naturally harbor this protein inside our bodies! Prusiner’s groundbreaking discovery won him the Nobel Prize in Medicine in 1997 [3].

If the prion protein exists in all of us, then why don’t we all have TSEs? It turns out that the protein is normally present in a harmless form called PrP C . Despite much work, scientists still are not sure what PrP C normally does in the body. However, what is special about this protein is that it can change from its normal shape into a misfolded shape (the prion form, named PrP-scrapie (PrP sc )) that can resist the harsh treatments that normally destroy proteins. In the prion form, the proteins aggregate, or clump, together and lead to brain damages by killing the neurons (brain cells) that harbor such aggregates. These aggregate protein clumps are also infectious and can spread to nearby cells and even to different individuals.

But how can proteins replicate and spread (a process which normally requires genetic material like DNA) on their own? It turns out that prions replicate by recruiting the normal PrP C proteins to the ends of the aggregates and forcing it to adopt the prion conformation as well. In this way, the prion aggregates will grow larger and larger over time (see Figure 1). When they get too large, they usually break into smaller aggregates, which can then go on to grow at the cost of the normal protein. This ability to corrupt the normal protein in the cell makes these prion aggregates infectious. A topic of ongoing research is the cause of the initial conversion of the protein, from its normal shape into prion.

Figure 1. A schematic of the two possible states of a prion protein. On the left, the protein is in its normal shape (PrP C ). In this state, the protein carries out a certain function in the cell. In the middle, the protein has converted to the aggregated prion form (PrP SC ). Prions have the ability to recruit normal PrP C proteins to the ends of the aggregates and convert them to prions as well. The aggregates grow larger in this way and when they get too big, they will break apart into smaller aggregates, which then convert even more normal protein to prions.

Making a lasting impression

Despite their bad reputation, recent research has shown that there is more to prions than initially thought. First, prions can be found in our primitive relatives, yeast and fungi, suggesting that they accompanied us during evolution. Also, not only do prions not kill the yeast cells that harbor them (contrary to what happens in mammals), but in harsh environments they even help yeast survive. For instance, research has shown that yeast strains that can form prions are more resistant to antifungal drugs or heat/chemical stress than strains that cannot form prions [4].

Prions could be beneficial in higher organisms as well, having been implicated in the process of memory formation. Neuroscientists have always been intrigued by our ability to form memories, and many believe that memories are encoded in the connections between neurons, called synapses. When we encounter an experience, neurons communicate with each other, strengthening their existing connections and establishing new ones, and this process is crucial to memory formation.

The “happens once and persists” feature of memory is loosely reminiscent of prions (once they form, they persist in the organism), and research in sea slugs has shown that there is a protein in the brain that behaves like a prion. This protein, called CPEB, can respond to an experience and facilitates the formation of synapses for storing the newly formed memory. CPEB is an unusual protein in the sense that it has the ability to form aggregates and replicate itself, just like a prion. However, unlike prions, CPEB does not cause neuronal death [5,6]. Researchers think that this prion-like behavior of CPEB may be important to its role in memory formation. Specifically, they think that in response to experience, this protein switches from its normal shape into the prion-like shape, which is better at making connections with nearby neurons and thus establishes memory in the brain.

So what should we make of prions-are they our friends or are they here to harm us? While more needs to happen, recent research suggests that we should keep an open mind and consider that there might be more to prions than a “spongy brain”.

Entela Nako recently finished her doctoral work in the Molecular and Cellular Biology Department at Harvard University.


What are Prions?

Prions are the infectious agents that cause Chronic Wasting Disease (CWD). Prions are abnormally folded proteins that lack DNA. They replicate by causing other normally folded proteins to rearrange themselves into a misfolded structure. The misfolded proteins accumulate in the brain, eventually leading to tissue damage and resulting neurological clinical signs and deficits.

CWD prions concentrate primarily in the brain, spinal column, and lymph nodes of infected animals. They have also been found, in much lower concentrations, in various other tissues and fluids.

Transmission of CWD

Deer can transmit CWD prions to each other through saliva, urine, and feces. This has led to restrictions on the feeding and baiting of deer in many states. Whenever deer are congregated, such as at a feed or mineral site, there is increased risk of direct (i.e., nose-to-nose) and indirect (i.e., interaction with saliva, urine, or feces contaminated with CWD prions) contact. Increased direct and indirect contact between healthy and infected deer may amplify disease transmission within a population of susceptible individuals.

CWD is considered an insidious disease for a variety of reasons, including the fact that infected deer may look completely normal for over a year before getting sick and eventually dying. During this time, they continually deposit infectious prions in the environment through their urine, feces, and saliva. Another complicating factor of CWD is the fact that prions may remain infectious in the environment for years, primarily in the soil. Because of this, CWD may be spread within a population by sick deer interacting directly with healthy deer and via contact with soil contaminated with prions.

Can Prions be Destroyed?

Prions are very hearty proteins. They can be frozen for extended periods of time and still remain infectious. To destroy a prion it must be denatured to the point that it can no longer cause normal proteins to misfold. Sustained heat for several hours at extremely high temperatures (900°F and above) will reliably destroy a prion.

Hunters are advised to wear gloves when handling deer carcasses and to clean equipment used on the carcass. While chemicals may not destroy a prion or render it inactive, prions may be manually removed or diluted with a disinfectant and scrubbing.

Prion Diseases

There are a variety of prion diseases, many of which only infect one species. CWD has only been documented in North American cervids, including deer, elk, moose, and caribou. Some prion diseases, such as Bovine Spongiform Encephalopathy, are able to infect multiple species.

Prion Disease Species Affected
Chronic Wasting Disease Cervids, including white-tailed deer, black-tailed deer, mule deer, elk, reindeer, and moose
Scrapie Sheep
Bovine Spongiform Dncephalopathy (a.k.a. Mad Cow disease) Bovines, humans (see New Variant CJD)
Transmissible Mink Dncephalopathy Mink
Creutzfeldt-Jacob Disease (CJD) Humans, occurs spontaneously, in 1 out of every 1 million people
New Variant CJD Humans, the result of BSE “Mad Cow” prions transmitted from a cow to a human
Kuru Humans, an extinct disease of Papua, New Guinea, spread through cannibalism

Incubation

Prion diseases vary in their incubation times. Most CWD research suggests incubation periods ranging from 16 months to four years, with an average of two years. CWD prions may remain infectious in soil for at least two years but likely longer.

Prion diseases found in humans (such as Kuru and Variant CJD) are known to have incubation periods of several decades. This possibility – a multi-decade incubation period – has always been a matter of great concern for researchers trying to determine if CWD prions can infect humans. Since CWD was first reported in wild elk in the early 1980’s, efforts to determine if humans are susceptible to CWD have to consider the possibility that it may be too soon for symptoms to have developed.

Treatment

At this time, there is no known treatment or vaccine for CWD. All animals infected with CWD will invariably die of the disease.


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Lichens vs. the Almighty Prion

And in this corner . . . the challenger, Lobaria pulmonaria. Given the common name "lungwort" thanks to its lung-like appearance, medieval herbalists invoked the Doctrine of Signatures to deduce it must be good for treating lung complaints. That is dubious, but it does seem to be good at something much more amazing. Creative Commons Jason Hollinger. Click image for original and license.

If you had to choose the world's most indestructible biological entity, it would be hard to do better than the prion. It's the Rasputin of biology: cook them, freeze them, disinfect them, pressurize them, irradiate them, douse them with formalin or subject them to protein-cleaving proteases, and yet they live.

Well, not literally live. After all, they're only proteins.

Prions -- infectious misfolded proteins -- have survived the pressure-cooker innards of autoclaves, the stout metal sterilizers that are the backbone of laboratory, hospital, and surgical sterilization. And they have survived for years in the punishing conditions of the outdoors -- wind, cold, rain, snow, ice, heat, and ultraviolet radiation.

These two points should strike fear in the hearts of mammals everywhere, for prions cause incurable fatal neurodegenerative wasting diseases and dementias of the worst imaginable sort -- the kind that swiftly strike down the hale and healthy in their prime.

If you are unfamiliar with prion diseases, that is only because you did not know they were caused by prions. In mammals: scrapie, chronic wasting disease, bovine spongiform encephalopathy, also known as mad cow disease. In humans: kuru, Creutzfeldt-Jakob Disease, and variant Creutzfeldt-Jakob Disease, a tidier name for, well, mad-cow disease.

Once symptoms appear in humans, tremors, convulsions, personality changes, hallucinations, and uncontrollable fits of laughter can precede death, usually within six months or so. Deer and elk slowly emaciate and glaze over mentally under the effects of the chronic wasting disease prion. Sheep with scrapie scrape the fleece from their presumably itchy backsides, and cattle with mad cow stumble around aggressively before succumbing.

Some of these diseases, in addition to their horrific manifestations, also have lurid origin stories. Kuru, for instance, plagued the Fore Tribe of Eastern Papua New Guinea thanks to their habit of consuming deceased members in order to return their life force to the tribe. Women and children were many times more likely to get kuru since the men appropriated the choice cuts, leaving them to eat less desireable bits like brain where prion particles congregate. Eventually authorities intervened to stop the practice.

Mad Cow, as you'll recall, was the result of farmers feeding their cattle ground-up dead cow(called "meat and bone meal"-- recall that cattle are herbivores), in which the prions causing bovine spongiform encephalopathy lurked. These, in turn, may have come from cross-contamination in slaughterhouses that also processed sheep with scrapie. When people in turn ate contaminated dead cow bits, to their horror, they too contracted the fatal wasting disease, and in Britain, at least 165 people died.

There was considerable controversy when the hypothesis that infectious proteins could cause disease was put forth, as the Central Dogma of Biology states that DNA is the unit of heredity and replication, and its bidding is done via RNA and then protein. That aberrant proteins could reproduce themselves, transmit disease and stir up trouble on their own without DNA's help seemed to violate this. When Stanley Pruisner won the Nobel Prize in 1997 for purifying prions, many remained skeptical (though in part because of his sloppiness as an investigator). Even now a few skeptics remain.

Still, the preponderance of the evidence seems to remain with the infectious protein hypothesis. How is it that this could work? Proteins can often change shape. Enzymes -- catalytic proteins -- and other proteins often undergo shape changes when substrates -- the molecules they act upon -- or other cofactors bind to them. These interactions are mediated by various bonds and charges, but to you and me, it looks like simple touch.

Usually these changes are reversible. But sometimes proteins can get stuck in misfolded, extremely stable conformations. What seems to have happened was that the normal prion protein at one point mutated in an individual in a way that changed its shape in an extremely unfortunate manner. Then this protein touched another protein of the same type, inducing a permanent shape change in it too and perpetuating the mistake. Like Pandora's box, once the chain of destruction was initiated, there was no going back.

In infected animals, the more proteins get stuck in the misfolded shape, the more are available to catalyze the reaction. It's exponential. Eventually, the buildup of malfunctioning proteins in sheets and fibrils called amyloid starts killing brain cells. Though the incubation period for prion diseases can be long, once symptoms emerge, the end usually comes nigher rather than later.

There is some controversy over how this happens -- do individual prions simply bump into other individual prions? or do they form long chains or sheets of a substance called amyloid (which you may recall is also a factor in many other neurodegenerative diseases like Alzheimer's) that break frequently and can catalyze reactions at either end? Regardless, the changes induced are permanent, the diseases incurable.

Recall that prions can persist on surgical equipment even after the sterilization of autoclaving. That's BAD. Since Creutzfeldt-Jakob disease in humans can occur spontaneously and the incubation period can be long, people may go into surgery not knowing they are a prion carrier. Scalpels, etc. have been contaminated and then autoclaved, only to spread the prions to helpless victims during subsequent surgery. This nightmare, has, in fact, really happened. New sterilization techniques have been decreed by the World Health Organization to prevent this, but it's a scary thought nonetheless.

In nature, animals have a similar problem. An elk with chronic wasting disease has saliva, urine, and feces full of prions that can linger in soil and contaminate green growth as it bursts forth in spring. When an infected elk dies, these prions are also released into the environment when the animals decay and can similarly hang out in places that elk like to feed. And, as mentioned above, they don't go away. While UV radiation and the extremes of heat and cold can peel paint and crumble newspaper, prions seem to shrug it off. Sheep and deer have indeed been infected after spending time in places contaminated years or decades ago. Since no evidence for a vector like a tick or mosquito exists, the prions seem to be going the same route cold-viruses take on day-care toys and doorknobs: the fomite, or inanimate object vector.

But there is one organism that seems to have found the chink in the prion's formidable armor: the lowly lichen.

Cladonia rangifera (likely), a reindeer lichen fed upon by their namesake, by Paul J. Morris. Creative Commons Click image for license.

Not all of them, mind you. But a few seem to produce a molecule -- likely a serine protease -- or molecules that can take out prions. And they may do it, surprisingly, because fungi seem to get prions too.

Scientists at the U.S. Geological Survey, the University of Wisconsin, Montana State University and the Universidad de Antioquia in Colombia investigated (and published the results in PLoS ONE) what, if any factors could promote prion degredation in the environment by looking at lichens -- fungal/algal/bacterial co-ops which are veritable fonts of chemical and molecular diversity. Lichens produce over 600 "secondary" compounds not essential to their metabolism. They make them for a variety of reasons, including defense from UV, microbes, and herbivory, and as water repellants. Many of these chemicals are responsible for their fantastic colors or fluorescence under UV or surprising color changes in reaction to other chemicals. You can spot a lichenologist in the field by the mini-chemistry labs they haul around for identification.

Since lichens are super-abundant in forest environments (despite the fact hardly any humans notice them), the scientists decided to put a few common lichens in the ring with prions and see who won. For reasons that are unclear to me but may include their abundance in deer and elk habitat, they chose Lobaria pulmonaria, the lungwort, a lichen indicative of pristine forest old-growth northern forests, Cladonia rangiferina, a member of a vastly successful genus common across North America, and Parmelia sulcata, likewise successful in the boreal forests of North America.

What they found was nothing short of stunning. Not only could lichen organic and water extracts degrade prions at least hundred-fold (and sometimes to the point of undetectability), simply incubating the prions in water with an intact lichen could destroy them -- mighty prions, which laugh off the rigors of autoclave and radiation, and I hardly need add, a slew of proteases we ourselves have thrown at them.

The researchers checked other species in the same genera, but these species lacked similar ability. They checked whether the algae the lichen fungi were partnering with were producing the lethal factor, and that seemed unlikely, at least when the algae were in isolation. They examined the effect of pH on the lichens' ability to destroy prion, and found that while P. sulcata's ability to degrade prions was pH sensitive (acidic was better), L. plumonaria's wasn't, suggesting they even have two separate ways of getting the job done -- suggesting that, if the effect is not just due to chance, lichens have figured out how to do this more than once, and it isn't even a big deal.

Parmelia sulcata, prion ninja. Creative Commons photo by James Lindsey at Ecology of Commanster. Click image for link and license.

Further testing suggested it was not one of three common lichen secondary compounds that was responsible, but in fact an enzyme called a serine protease, since only serine protease inhibitors were capable of destroying lichen extracts' prion-fighting powers. Proteins are built of long strings of amino acids, proteases are enzymes that cleave other proteins, and serine proteases have the amino acid serine in their active sites, the seats of catalysis. Why lichen serine proteases can cleave prions where so many other proteases have failed is not known. It's also unknown, the scientists noted, whether some other lichen chemical or protein may be acting as a co-factor that helps the serine protease do its job.

Could lichens provide the same services in nature? Could prions that land on or near lichens whose chemicals may leach out by rainwater reach their ignoble end at last?

It's also unknown why lichens might possess this unlikely ability. Yeast -- fungi that have reverted to a single-celled lifestyle -- are known to have prions with amino acid sequences different from the mammalian prions but similar overall sheet-like amyloid structures.They may induce disease sometimes, but in other cases, they may confer an advantage on their hosts by permitting sharing of resources only between individuals that are sufficiently genetically similar.

No one has checked lichens for prions. But since the overall shape of known fungal prions resembles mammalian prions, the researches suggest it's possible lichen proteases could act against fungal prions and mammalion prions alike. Whether putative lichen prions are as destructive as the mammalian forms -- or even if they might be beneficial -- remains in question, but the fact lichens have them suggests prions might be something that lichens are happier without.

You may wonder if lichens could be used to help protect humans from our own prion diseases. This is probably not feasible in surgical environments, both because lichens seem not to achieve complete degradation of prions reliably and because a nuclear option exists: Bleach or sodium hydroxide. Lots of bleach or sodium hydroxide (followed by autoclaving). Bleaching the forest is less feasible. Lichens, however, may be a built-in distributed defense system we didn't even know we had.

Johnson CJ, Bennett JP, Biro SM, Duque-Velasquez JC, Rodriguez CM, Bessen RA, & Rocke TE (2011). Degradation of the disease-associated prion protein by a serine protease from lichens. PloS one, 6 (5) PMID: 21589935

The views expressed are those of the author(s) and are not necessarily those of Scientific American.

ABOUT THE AUTHOR(S)

Jennifer Frazer, an AAAS Science Journalism Award–winning science writer, authored The Artful Amoeba blog for Scientific American. She has degrees in biology, plant pathology and science writing.


How prions kill brain cells

Brain-wasting proteins called prions kill neurons by shortening the dendritic spines that the cells use to transmit signals to each other.

Prions are infectious and cause neurodegenerative diseases such as scrapie in animals and Creutzfeldt–Jakob disease in humans. To learn how they kill brain cells, David Harris at Boston University in Massachusetts and his co-workers exposed cultured mouse neurons to the prion that causes scrapie in mice. They found that the neurons' dendritic spines retracted within 24 hours, before the cells died. This occurred only in neurons that made the normal, non-infectious form of the prion protein, which suggests that the disease-associated prion might bind to the normal one to trigger dendritic loss.

This method could be used to test potential drugs against prion diseases, the authors say.


Can People Get BSE?

People can get a version of BSE called variant Creutzfeldt-Jakob disease (vCJD). As of 2019, 232 people worldwide are known to have become sick with vCJD, and unfortunately, they all have died. It is thought that they got the disease from eating food made from cows sick with BSE. Most of the people who have become sick with vCJD lived in the United Kingdom at some point in their lives. Only four lived in the U.S., and most likely, these four people became infected when they were living or traveling overseas.

Neither vCJD nor BSE is contagious. This means that it is not like catching a cold. A person (or a cow) cannot catch it from being near a sick person or cow. Also, research studies have shown that people cannot get BSE from drinking milk or eating dairy products, even if the milk came from a sick cow.


Resistant Prions: Can They Be Transmitted By Environment As Well As Direct Contact?

Prions, the pathogens that cause scrapie in sheep, can survive in the ground for several years, as researchers have discovered. Animals can become infected via contaminated pastures. It is not yet known whether the pathogens that cause BSE and CWD are equally resistant.

A flock of sheep at pasture &ndash a seemingly idyllic scene. But appearances can be deceptive: If the animals are suffering from scrapie, entire flocks may perish. Scrapie is an infectious disease in which prions destroy the animal&rsquos brain, rather like BSE. The brain becomes porous, the sheep lose their orientation, they suffer from strong itching sensations and scrape off their fleece. Eventually, the infected animals die.

It is difficult to contain the disease &ndash all too often, scrapie will break out again on the same farm several months or years after it has apparently been eradicated. Are the prions transmitted not only by direct contact, but also by the environment &ndash perhaps by the pastures? How long do prions that get into the pasture via the saliva and excrements of the sick animals, persist in the ground?

Together with fellow-scientists from the Robert Koch Institute in Berlin and the Friedrich Loeffler Institute (Federal Research Institute for Animal Health) on the island of Riems, research scientists from the Fraunhofer Institute for Molecular Biology and Applied Ecology IME in Schmallenberg investigated these questions on behalf of the German Ministry for Environment, Nature Conservation and Nuclear Safety BMU.

&ldquoWe mixed soil samples with scrapie pathogens to find out how long the pathogens would survive,&rdquo says Dr. Björn Seidel, who headed the investigations at IME. &ldquoEven after 29 months, in other words more than two years, we were still able to detect prions in the soil.&rdquo

But are these prions still infectious? &ldquoThe soil actually seems to increase the infectiousness of the pathogens. The incubation period &ndash the time it takes for the disease to break out &ndash is exceedingly short even after the prions have persisted in the soil for 29 months. All of the animals that were given contaminated soil became sick within a very short time. These results indicate that fresh incidences of scrapie among sheep are due to contaminated pastures,&rdquo says Seidel in summary.

The results of the study reveal that sheep may even become infected from the surface water, though the risk of infection is much lower in this case. There is no danger to humans, however: scrapie pathogens seem unable to affect them.

Another cause for concern is chronic wasting disease (CWD). Like BSE and scrapie, this is caused by prions, but it mainly affects deer. The numbers of infected animals in North America are rising steeply. How long do BSE and CWD prions survive in the ground? &ldquoTo find this out, we urgently need to carry out further tests. The appropriate research applications have already been submitted,&rdquo says Seidel.

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Materials provided by Fraunhofer-Gesellschaft. Note: Content may be edited for style and length.


UV-light-induced conversion and aggregation of prion proteins

Increasing evidence suggests a central role for oxidative stress in the pathology of prion diseases, a group of fatal neurodegenerative disorders associated with structural conversion of the prion protein (PrP). Because UV-light-induced protein damage is mediated by direct photo-oxidation and radical reactions, we investigated the structural consequences of UVB radiation on recombinant murine and human prion proteins at pH 7.4 and pH 5.0. As revealed by circular dichroism and dynamic light scattering measurements, the observed PrP aggregation follows two independent pathways: (i) complete unfolding of the protein structure associated with rapid precipitation or (ii) specific structural conversion into distinct soluble beta-oligomers. The choice of pathway was directly attributed to the chromophoric properties of the PrP species and the susceptibility to oxidation. Regarding size, the oligomers characterized in this study share a high degree of identity with oligomeric species formed after structural destabilization induced by other triggers, which significantly strengthens the theory that partly unfolded intermediates represent initial precursor molecules directing the pathway of PrP aggregation. Moreover, we identified the first suitable photo-trigger capable of inducing refolding of PrP, which has an important biotechnological impact in terms of analyzing the conversion process on small time scales.