Talk:Prion

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The citation is in: "ذره پروتئینی شگفت‌آور The Wonderful Proteinaceous Particle", Shargh, February 1, 2004.

Peer review This article was externally reviewed on December 14, 2005 by Nature. It was found to have 7 errors.

Contents

[edit] The first paragraph is currently plain wrong

I am not an expert, but the article does not make sense. The truth is the "badly folded form" propogates by causing other forms to refold. But if the badly folded forms are called prions, and also the other forms are called prions, then the paragraph is inaccurate as now worded.

[edit] Exotic Ungulates

Can anyone state a good reason to separate one kind of hoofed animal from another? Brewhaha@edmc.net 09:18, 30 November 2006 (UTC) The section on exotic ungulates is currently red, because it's not in the wiki. Brewhaha@edmc.net 09:18, 30 November 2006 (UTC)

[edit] Dissent deletion

should the section

"(This isn't dissent per se. It's merely an alternative model for the initial acquisition of Prion related diseases. Its relevance and specificity to bovines is questionable and possible it is more relevant to murine disease acquisition. How it relates to the BSE epidemic is hard to fathom, it certainly may play a role in disease acquisition, however, the plague like transmission is overwhelmingly attributed to the consumption of infectious material. To title this section dissent is kind of baffling as there are many other occurrences which result in the initial incidence of the disease, but none of these account of the aformentioned epidemic. Furthermore, the models which do explain PrP formation biochemical models are just that, biochemical models, proven in a laboratory. They certainly are not epidemiological studies used to build models in the absence of experimental work.)"

even be in the article? it reads more like a forum post replying to the previous paragraph than something that belongs in wikipedia-Lehk 05:23, 8 September 2006 (UTC)

[1] I tend to think not. It is like a forum post, as you say, but more agreeable than most I've dealt with. Whoever wrote it is trying to find a way to the touted neutral point of view. Brewhaha@edmc.net 09:18, 30 November 2006 (UTC)

I don't see the point of this section either - Purdy and Brown have not "dissented" to the existence of prions, they've just expressed some different ideas about the role of metal-binding. There is no controversy over whether PrP binds metal cations or whether these can somewhat influence PrP structure. David Brown places a lot of emphasis on his proposal that metal binding gives PrP enzyme activity and that abnormal binding might lead to a disease state, while Mark Purdy, who was a farmer by profession, was interested in differences in metal ions in the soil and a possible relevance to BSE. Brown was the only established prion researcher who took Purdy's ideas seriously, while Brown's ideas are interesting but have not quite become 'mainstream' and are still mostly considered speculative. I don't really see why these two interesting but minority views warrant a section to themselves. Purple 12:32, 3 January 2007 (UTC)

The question is not a popularity contest. I moved the section that referred to "protein-X" before I saw this comment, and I hope you can see that it fits into dissent. I read of other causes for dissent in a Nature article. Perhaps I left a reference to it on the talk page about TSEs. As for the FAQ format? I think that should sit for a while. Brewhaha@edmc.net 15:43, 20 February 2007 (UTC)

[edit] Division of Topics

-- FFI is more relevant to TSEs. Brewhaha@edmc.net 09:18, 30 November 2006 (UTC)

Fatal Familial Insomnia is genetic. But it is inherited as a one base mutation on the same gene that synthesises PrP, the prion protein. I do not know if attempts to infect organisms with FFI have been successful.

In FFI patients, PrPSc is often not detectable in the brain, yet the disease is transmissible (Tateishi et al., 1995;Collinge et al., 1995) Pikzee 18:04, 21 March 2007 (UTC)


I must also add that a lot of information on prion actionmechanism is speculative. The evidence of prions being infective agents is not yet conclusive. The final "proof" will be infectivity initiated by injection of synthetically produced prion material into an organism. This would be the only way to ensure that no other agents have been introduced. A vocal scientific minority still opposes this.

I think therefore that this article needs a rewrite to take into account these issues. Also a list of references will be useful. I am not competent enough to do this due to lack of biology knowledge. I will add a few external links with more info.--Viz

It seems that an artificaial prion HAS been created:

http://www.nature.com/news/2004/040726/full/040726-11.html

[edit] Stability of Vector

What puzzles me is how prions can survive extreme conditions (e.g. autoclaving) that clearly are capable of denaturing proteins. This suggests that something is missing in our understanding of this phenomenon. Beyond that, there are certainly many factors that will influence the folding of proteins. It would seem possible, likely even, that many proteins have alternative folding configurations, and that many non-fatal and less obvious diseases (less obvious compared to CJD) may have their basis in problematic protein folding. --BL

Denaturation is essentially a type of refolding. Other proteins are difficult to heat denature as well--especially short ones. Dogface 05:01, 6 Apr 2004 (UTC)

The beginning of paragraph two mentions "mysterious infectious agents" and then has these agents in the singular; visiting the Creutzfeldt-Jakob Disease revision history shows that this part did indeed refer specifically to the prions causing C-JD so I've clarified it as such here. --KQ

Isn't fatal familial insomnia genetic? --LDC

[edit] Spelling of Deutschenamen

is it really Creutzfeldt? I thought it was spelt with a "K"

All of the references I checked spell the names as "Hans Gerhard Creutzfeldt" and "Alfons Maria Jakob". Both are German, and I agree that the initial-C looks odd for a German name, and "Creutz" is not a German word I'm familiar with. Maybe he has a different ancestry or something.

It is Creutzfeldt, from "Kreuz" meaning cross and "Feld" meaning field. As you noticed, the spelling is not correct in today's German, but that is not unusual in names, as they often date back some centuries. Also, "Maria" isn't a usual name for boys these days anymore (except Klaus-Maria Brandauer). --Magnus Manske

[edit] Wiki technique

Somebody turned this page into a disambiguation page and then didn't bother to fix any links to point to the new pages (per our disambiguation guidelines). So I moved this page back to fix the links and added a disambiguation block to the top of this page. --mav

[edit] Prion/Comments

Welcome to Wikipedia! We welcome your help to create new content, but your recent additions (such as Prion/Comments) are considered nonsense. Please refrain from creating nonsense articles. If you want to test things out, edit the sandbox instead. Take a look at the welcome page if you would like to learn more about contributing to our encyclopedia. Seinfreak37 17:24, 20 February 2007 (UTC)

I think you'd better double-check that. You can find the word "here" at the top of this page where it tells you where to write why you might want to rate a page good. Brewhaha@edmc.net 15:15, 22 February 2007 (UTC)

[edit] Ist es logish?

If N and P were really made by fork of a normal metabolic pathway, and P would cause negative feedback on N in this process, every organism would quickly infect itself without external P's; it would be sufficient to produce some P's "normally".


[edit] More on Vector Stability

The pathogen thought responsible for this disease is not a virus, not a fungus, not a bacteria, but thought to be a prion — an infectious protein. Because of their unique structure, prions are practically invulnerable. They can remain infectious for years in the soil. They are not adequately destroyed by cooking, canning, freezing, usable doses of radiation, digestive enzymes or stomach acid. Even heat sterilization, household bleach and formaldehyde sterilization have little or no effect. One study raised the disturbing question of whether even incineration could guarantee the inactivation of prions.

That study was performed by Paul Brown, medical director for the U.S. Public Health Service, who found prions could remain infectious even after exposure to temperatures over 1000 degrees Fahrenheit. That's hot enough to melt lead. Prions have been called the smallest, most lethal biological entities in the world. [2]

I think you should take a look at this study's abstract: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14697205

[edit] Self-Replication or propagation of Shape

If prions can influence mRNA translation, then prions would be neither self-replicating nor exceptions to the so called central dogma of modern biology, but proteins that regulate mRNA translation (at least). That is, if prions do not modify their inactive "cousins" (same primary structure or aminoacids sequence, but diferent subsequent structures due to different folding) in the absence of nucleic acids (something that to the best of my knowledge has not been found).

Also, why do you say that the modification of the struture of a protein does not modify its properties (in particular biological, but those are dependant on the shape of the protein and thus all derivated properties -that is, known characteristics- are modified more or less)? That is why by heating to high temperatures (specially in a forceful manner to proteins whose shape is dependant on low energy bonds) enzymes can be deactivated (rupture of these bonds) and also why if the peptide bonds were not broken it is possible that the enzyme will reactivate (reestablish low energy bonds).

I am by no means studying prions (and so i cannot assure you that it han not been shown that prions can modify their "cousins" in the absence of nucleic acids) but i beleive it is a whortwhile question.

Bernardino

Just because a prion can influence mRNA translation does not mean it's not self-replicating. Also, a prion isn't quite a family of proteins in the same way as say, kinases are. Generally, prion proteins have a normal function, but 'on the side', they have the capability to aggregate and propagate in the prion state. In fact, for several prion proteins, prion propogation actually results in a partial loss of function phenotype.

To address your second question, it was recently shown that URE2, a yeast prion, will form orderd aggregates in vitro at a neutral pH, and that these aggregates retain their infectivity. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16096644&query_hl=16

From what I see, the violation of the central dogma comes from the fact that prions propogate by modifying the conformations of their cousins. I guess I don't really understand how requring nucleic acids to hang around would prove that prions follow the central dogma.

Morwan


Okay, so prions can survive temperatures of up to 1000 degrees Fahrenheit. Exactly how does their structure allow them to do this? How are they invulnerable to things like cooking and stomach acid? All proteins should be broken down in your body cells! Scorpionman 00:42, 3 May 2005 (UTC)

One explanation could be the independance from fragile bonds, if they were a short protein without cuaternary or tertiary structure they would be much harder to modify in their tridimensional structure (it would only have peptidic and hydrogen bridge bonds). As a matter of a fact, in the absence of highly specific enzymes, many compounds are not broken down even in extremly acid conditions (remember lactose for example, it is a short sugar, disacaride, it is not broken down withouth lactase and so it is not asimilated, however, that birngs the question on how did the protein enter then if it was to big?, just thinking that maybe it is not just size what matters but shape and this protein could somehow be asimilated despite its size, or maybe it is broken but espontaneuosly reforms, something that seems to me very unlikely unless it is a very short protein indeed -like two or three aminoacids-).

Take all this as thinking aloud with VERY LITTLE to think on, I do not consider to be in a position to understand this becuase I have not experimentated with prions nor reviewed enough to consider it to be a significant amount of what is needed to understand this.

Bernardino

You said that 1000 degrees Fahrenheit is hot enough to melt lead. True, but lead doesn't require that high a temperature to melt. It's melting point is so low that it can melt in a wood fire. Anyway, prions aren't really alive, so you can't "kill" them essentially. You would have to use a very complicated process to take them apart. Scorpionman 17:43, 19 November 2005 (UTC)

[edit] New synthetic prion

I'm not expert enough on this to do the following justice. Anyone care to add a section on the synthetic prion developed that causes similar brain deterioration in mice? http://www.cnn.com/2004/TECH/science/07/30/syntheticprotein.ap/index.html - Tεxτurε 20:00, 30 Jul 2004 (UTC)

I've read Stan Prusiners original publication on the "synthetic" prion. While the article gives strong support for the prion hypothesis, there are some issues regarding the design of the experiment. Especially the use of mice which overexpressed PRNP about 16-fold is a critical point in the study. I'd like to let the whole thing settle in for a while before adding this information to the article. Dr. Strangelove 13:39, 6 Aug 2004 (UTC)

brewhaha@ecn.ab.ca: I would favour ignoring that for the jenetik content in artificial mutants, except such things might also hav changes in their metal metabolism. Then again, artificial mutants aren't designed to live in the real world. In the article about TSEs, it goes into more detail about jenetiks, where it should. Maybe that's a better place to discuss synthetic normal prions. 216.234.170.83 06:41, 16 July 2006 (UTC)

I think it's worth mentioning in the article that the word prion is pronounced "PREE-ON" instead of "PRY-ON" as most people assume... minor detail, but very important to avoid embarassing situations. Brodo 08:14, 19 Mar 2005 (UTC)

brewhaha@ecn.ab.ca: No matter what the coiners of the word say, I think the etymology "protein ion" (and pronunciation: pry-on, after ion) fits the spelling and meaning of the word more aptly. Noting the interference from jenetiks on this topic, I'm inclined to remove any divergence into the topic. No nucleic acid. No artificial mutants. I think the notes about autoclavure paint a very sharp picture against this group of diseases being caused by protein, too. At 1000 degrees F, protein doesn't just denature. It decomposes. Changes in protein are an EFFECT. I suspect that a metal ion (manganese?) is flattening the protein.

The Oxford Dictionary of Phrase and Fable excludes things from the definition of prion like this: prion ... Prions are not visible microscopically, contain no nucleic acid, and are highly resistant to destruction.

Is the Phoenix more than fantasy? Can you blame what you cannot see and name it matter of muscle?

Ions of protein or life you cannot blame. It follows that poison is cause of the lame. 216.234.170.83 06:41, 16 July 2006 (UTC)

[edit] synthetic prions - not quite

The claim by Prusiner's group to have infected mice with synthetic prions is not as clear-cut as it seems. The mouse line used already had a mutation in its prion protein that causes prion disease. They say around 70% of the animals don't show symptoms within their lifetime, but this does not mean the infectivity is not there; they will have sub-clinical infection.

What they did in this research is to take some synthetic prion protein, containing the same mutation, fold it into a beta sheet form, and inject it. However, it has been shown that you can take an animal with pre-clinical amyloid disease, inject some beta-sheet protein (of any sort) and the disease will be accelerated so that they show symptoms much quicker. The beta-sheet protein seems to 'seed' the pre-existing amyloid so that the disease progresses faster. The research done in this paper is not novel - similar results have been reported before.

The true holy grail of prions is to take some pure, recombinant, wild-type PrPC, do something to it, then inject it into a wild-type mouse, and cause disease. Nothing close to this has been achieved, though I think it will be at some point. --Purple 01:48, 19 May 2005 (UTC)

[edit] Prion Terminology

The term prion isn't clearly defined in the article, it seems to suggest that prion proteins exist solely to aggregate, and do not have any normal cell function.

Morwan 18:50, 22 December 2005 (UTC)

Early in the history of the article, I had added a sentence to suggest that prions may be thought of as auto-chaperone's. I thought that was a fairly good way of defining prions in terms of what was already known. [3]. Many other papers suggest the connection between prion and chaperone proteins. Unfortunately I am not an expert on the subject :( Shyamal 06:30, 31 January 2006 (UTC)

[edit] Errors ID'd by Nature, to correct

The results of what exactly Nature suggested should be corrected is out... italicize each bullet point once you make the correction. -- user:zanimum

  • It should first be clearly stated that prions replicate through conversion of the host normal prion protein (and not any other host protein).
  • It is untrue that prion domains are flexible and lack a defined structure. On the contrary, prion domains are fold into structures called alpha helices in the normal conformation and are stretched into flat structures called beta strands when in the "prion" state.
  • Unclear: Regarding the normal cellular prion protein, its precise location is at the surface of all cells. It is untrue that its function is not known, rather it is not completely resolved.
  • Unclear: Concerning propagation of prions, it is not the disease which is propagated but the infectious agent (prions).
  • The sentence linking prions to memory and cellular differentiation is extremely misleading. The normal function of cellular prion protein in mammals is not fully understood, but it may take part to cell adhesion mechanisms, cell signaling, copper homeostasis, and protection against insults such as oxidative stress.
  • Bias; A very (too) long part of the entry is about yeast prions, as compared with mammalian prions. The occurrence of prions in yeast is interesting in so far as it gives credence to the protein only hypothesis.
  • It also has allowed to shed some light on the prion domains (i.e. regions in the protein involved in the conversion) and on the mechanisms of conversion. However, it is untrue that prion-like proteins are found in "many" plants or animals (we just do not know). The word "useful" is also confusing, while it is true that not all prions are associated with a "disease" state.

--Purple 02:49, 2 February 2006 (UTC)


In order to resolve the 'bias' issue, would it be best to split off the prions in model organisms into its own article? I still think that prions in model organisms should be an integral component of this article: Sup35p has been studied for decades and may be considered the 'best-understood' prion. An expansion of the mammalian section of the article should be done, obviously. Maybe the tables are a bit too much information for a general article... Maybe those should be placed in seperate articles?

Someone want to help me work on a yeast/model organism prion page?

Morwan 23:48, 22 December 2005 (UTC)

[edit] Revisions post Nature review

As a major contributor to this article, I feel as if I should chime in on the Nature review, which was generally fair and helpful.

-It should first be clearly stated that prions replicate through conversion of the host normal prion protein (and not any other host protein).

-Noted and corrected

-It is untrue that prion domains are flexible and lack a defined structure. On the contrary, prion domains are fold into structures called alpha helices in the normal conformation and are stretched into flat structures called beta strands when in the "prion" state.

-Clarified that this section refers to yeast prion domains, not to PrP. However, only a part of the Prp-C conformation is alpha-helical; major portions of the protein's structure have not yet been defined.

-Unclear: Regarding the normal cellular prion protein, its precise location is at the surface of all cells. It is untrue that its function is not known, rather it is not completely resolved.

-Noted and corrected

-Unclear: Concerning propagation of prions, it is not the disease which is propagated but the infectious agent (prions).

-I've clarified this point to make it clear that the infectious agent is replicated, propagating the disease state between cells and (potentially) animal hosts.

brewhaha@ecn.ab.ca doesn't think this is a big deal at all. If the phenomenon wasn't a disease, then it wouldn't involve an infectious agent. Someone is splitting hares. 216.234.170.85 12:55, 14 July 2006 (UTC)

-The sentence linking prions to memory and cellular differentiation is extremely misleading. The normal function of cellular prion protein in mammals is not fully understood, but it may take part to cell adhesion mechanisms, cell signaling, copper homeostasis, and protection against insults such as oxidative stress.

-I've always been skeptical about the Lindquist and Kandel papers linking learning in Apleisa with a prion mechanism. I agree with the reviewer that this discussion point should be deleted.

-Bias; A very (too) long part of the entry is about yeast prions, as compared with mammalian prions. The occurrence of prions in yeast is interesting in so far as it gives credence to the protein only hypothesis.

-I disagree. The yeast prion field is miles ahead of the mammalian prion field, and unlike the mammalian prion diseases, fungal prions are wide-spread in nature, diverse in protein sequence and function, and potentially are adaptive rather than pathological. Readers interested mammalian prions can click through to the many TSE links.

-It also has allowed to shed some light on the prion domains (i.e. regions in the protein involved in the conversion) and on the mechanisms of conversion. However, it is untrue that prion-like proteins are found in "many" plants or animals (we just do not know). The word "useful" is also confusing, while it is true that not all prions are associated with a "disease" state.

-I disagree (see [4]) and have added this citation to support this claim

I've updated the error table in the outside review article to indicate that the requested revisions have been completed.

yeastbeast

The word "replicate", when talking about prions, is not very appropriate. The replication is a very complex process, involving many different molecules, reactions, and is under some type of error check, it is not a mere switching from one stable protein conformation to another. "Self-propagating" used by the authors of

this article, for which you have provided the link, is a lot better.

[5]: Thinking about that a bit more, "propagation" alone, of the trait might work nicely, because I'm getting the impression that "replication" is reserved for jenetiks. 216.234.170.74 13:23, 31 July 2006 (UTC)

This text (in the "Into" section):
that prions are responsible for a number of previously known but little-understood diseases generally classified under transmissible spongiform encephalopathy diseases (TSEs)
, and the text at the end of the "Prion hypothesis" section"
The degenerative diseases caused by prions are known collectively as "transmissible spongiform encephalopathies" or TSEs
say almost the same thing.

brewhaha@ecn.ab.ca agrees. Why repeat yourself with LESS detail? 216.234.170.85 12:55, 14 July 2006 (UTC)


This text:
Because of this, scientists reasoned that such proteins could give some sort of evolutionary advantage to their host. - is crap, of coooourse THEY DO, otherwise why loose the genes for the synthesis of the very important vitamin C and keep the ones for the "nasty" prions, plz remove this "great reason of the human mind" of whoever-said-it. I'll see if i can contribute a bit. -- Boris 18:50, 25 December 2005 (UTC)

brewhaha@ecn.ab.ca says that it definitely bears repeating that genetics were ruled out of the prion hypothesis at inception. They therefore hav nothing to do with a major difference between rats and humans. <opinion> The artificial mutants with a predisposition to produce pathological protein probably hav a difference in their sensitivity to an elemental poison -- a difference in their metabolism of an element. </opinion>216.234.170.85 12:55, 14 July 2006 (UTC)

About the advantage thing, even if it's blatantly obvious, there might be layreaders who wouldn't come to that conclusion. -- Natalinasmpf 22:20, 25 December 2005 (UTC)

Yeah you are right, but it also makes those whoever-sayers look stupid in the no-layreaders eyes. -- Boris 22:59, 25 December 2005 (UTC)
Maybe you could be bold and find a better way to phrase that passage? :) - Samsara 02:07, 7 January 2006 (UTC)

I also disagree with the reviewer's comment that yeast prions are less interesting than mammalian prions - I think this is itself a biased opinion. Yeast/fungal prions are a very different phenomenon to mammalian prions, i.e. fungal prions are a completely new mechanism of epigenetic inheritance involving many species/proteins, while mammalian prions are just related to a limited range of diseases. I can therefore see why it's difficult to discuss them both in the same article, I think there's an argument for having separate bits for prions (disease) and prions (regulatory mechanism). Not sure how that would work though...--Purple 19:16, 22 January 2006 (UTC)

[edit] Genetic material

As written, the Genetic material article seems to imply that prions are living organisms and have genetic material that is not DNA. --JWSchmidt 22:36, 25 December 2005 (UTC)

I've done my best on that article, but someone needs to add the names for normal and evil prion to complete the exposition. - Samsara 02:03, 7 January 2006 (UTC)

[edit] prion strains

Hmmm the first section explains what a prion is, then later on there's a table of different prion isoforms, with no explanation of what a prion isoform is or how one protein can cause all those diseases. Maybe we need a section explaining prion strains, especially since the existence of strains is one of the things that prion-sceptics get most twitchy about. --Purple 14:27, 22 January 2006 (UTC)

brewhaha@ecn.ab.ca: This Flat Earther isn't twitchy about prion strains at all. If I ignore the topic, then jeneticists will eventually occlude the theory of self-propagating protein deformation with a theory of inheritable disease. If I don't ignore it, then I'll find evidence that the strains are malleable, meaning that manipulating the salts of their solution will change their strain. 216.234.170.83 07:06, 16 July 2006 (UTC)

Some references for prion "strains". These "strains" seem to be in some way related to structural/conformation variations in the prion protein.

--JWSchmidt 15:38, 22 January 2006 (UTC)

Anyone got any objections to me sticking a section in? However it would be from the point of view of mammalian prion disease only unless someone else can do yeast strains--Purple 19:18, 22 January 2006 (UTC)

A discussion of strains would be quite helpful. If Purple wants to add a bit about the PrP strain phenomenon (distinction between FFI, CJD and GSS, for instance) I could add a bit about conformational variation in [PSI+] yeast prions (my area of specialty). However, the article is now a bit disjointed with the bulk of the yeast prion information in a separate article, yet retaining the technical discussion of yeast prion structural features. Perhaps prion strains should be a small, non-technical section with a link to a more comprehensive article. Yeastbeast 08:30, 29 January 2006 (UTC)

brewhaha@ecn.ab.ca: I must've gotten the idea for putting most of the jenetics under TSEs from you. 216.234.170.83 07:06, 16 July 2006 (UTC)


One of the most remarkable features of prion disease is the existence of distinct prion strains with well-defined heritable properties. These strains were originally characterized by incubation time and resultant neuropathology (Bruce et al., 1992), but they can also be differentiated on the basis of PrPSc distribution in the brain and physicochemical properties of PrPSc such as resistance to proteases and how they have been glycosylated - their 'glycoform ratio' (reviewed in: Bruce et al., 1996). As different prion strains can be serially propagated in mice with the same Prnp genotype, they can not be encoded by the primary sequence of PrP. It is now thought that strain specificity is determined by PrP conformation and glycosylation. Different PrP conformers could interact with varying efficiencies and glycosylation may influence where in the brain a strain may target (Collinge et al., 1996;DeArmond et al., 1997). It is known that different cell types may glycosylate proteins differently, therefore particular PrPSc glycoforms might replicate most favourably in those cells expressing a similar PrP glycoform. This regional targeting could also explain the differences in incubation times between various strains with targeting of more critical brain regions resulting in shorter incubation periods. Pikzee 17:35, 21 March 2007 (UTC)

[edit] PRP acronym

"Prion-related protein"? I thought PrP stands for Protease-Resistant Protein. Someone please clarify and maybe even make an appropriate link from the acronym disambiguation page PRP. Alex.g 17:04, 17 February 2006 (UTC)

Yes I think that was how PrP got its name originally, but that was before people knew it also came in a 'normal' form. So by general consensus it's now known as 'prion protein' (now I think about it no-one really refers to it as 'prion-related' protein). I suppose that could go in the article for thoroughness. --Purple 03:17, 18 February 2006 (UTC)
Yes, when Stanley Prusiner did his studies in 1982, he found the DNA sequence that codes for the prion that causes scrapie and CJD. He called the protein a PRP (protease-resistant protein). I don't believe that it has changed meaning since then, since the term is still accurate. --Bona Fide 10:23, 4 March 2006

brewhaha@ecn.ab.ca My orijinal impression of the word, "protein ion", (which I pronounce pry-on, despite Webster and the IPA, which disagree, so that I'm tempted to delete one or fix the other) relates to the binding of copper to it as if the protein wer charjed. I'm using flat prions for sick prions and I'll use twisted prions for healthy prions if it comes up. Burn the alphabet soup.216.234.170.85 22:16, 14 July 2006 (UTC)

[edit] How does it stay 'alive?'

Biology is not my strong point, but when a cow dies of BSE, and if its remains are eaten by another cow, should the Prion protein not have been destroyed when the original cow died (maybe by proteolysis) and should it not be digested in the other cow's stomach? I just don't get how the endogenous Prion still sits in its abnormally conformed shape even after the host has died? Anyone?

Prions aren't affected much by proteolysis or anything else. Otherwise the animal would be able to break them down when it's alive. You can put prions in formaldehyde, boil them, in fact boil them in formaldehyde if you like, whatever - they survive a lot of stuff (their structure is very stable) --Purple 03:42, 10 March 2006 (UTC)
~ User:Unfortunate


[edit] Lamarkian evolution

Can prions really be said to instance the inheritance of acquired characteristics?

brewhaha@ecn.ab.ca doesn't think so. If I'm not mistaken, the only vector for acquired characteristics other than the DNA of your cells is the DNA of your mother's mitochondria, which come strictly from your mother, and these prions haven't been shown to influence DNA. They are not mutajens. 216.234.170.85 12:55, 14 July 2006 (UTC)

I am certainly not expert in this field but I think I understand this article to say that PrPSc is a protein coded for by dna as is any other protein.

The fact that the form of the prion is in some way contagious does not affect the offspring of an infected organism, one whose dna does not itself code for the prion itself, or does it? Jfmxl 03:29, 28 March 2006 (UTC)

brewhaha@ecn.ab.ca: That's another vote for somehow making it clear that this topic is not about genetics without deleting references to genetic experiments, which is exactly what I would do if this were a personal web page. DNA codes for prions, and it doesn't encode their shape. I hope that's a principle, because I'm looking for a way to find it. Hmmm. DNA does not encode the folding or shape of protein. It seems to be false according to the part about jenetiks under TSEs, but I can't rule out the possibility that the prions it is talking about involve a different amino acid sequence. 216.234.170.83 07:14, 16 July 2006 (UTC)

  • I'm not so clear on the justification for mammalian systems, but with fungal prions it's pretty obvious that prions are acting as epigenetic elements. Two genetically identical cells will have significantly different phenotypes depending on their prion state. Once a cell becomes PRION+ (prion proteins are aggregated), it and virtually all of its offspring will be PRION+. Occasionally there is reversion to a prion- (not aggregated) state, but it's extremely rare. Morwan 08:51, 28 March 2006 (UTC)
brewhaha@ecn.ab.ca: Rare, you say? Take an empty two litre bottle of pop. Put 2/3 cup of molasses and 1.25 litres of water in it. Sink a cap of your favourite fungus into it. You'll get non-aggregated yeast, or perhaps semi-aggregated yeast. Take out the cap. Dump the liquid into a pail of sawdust or grass clippings. You'll get aggregated yeast: caps. 216.234.170.83 07:14, 16 July 2006 (UTC)
  • PrP is a protein sequence coded by DNA as any other protein. PrPC is native folding state of this protein (unfortunately I have no information in function of PrP, but it should have some functions in organism as we all have this protein). PrPSc is different folding state of PrP - it has different secondary structure and aggregates forming amyloid fibrils. PrPSc is not native state of PrP and appears only because of special conditions - like mutations or presence of already formed PrPSc which pushes PrPC to change structure. V.S.

[edit] Is Prion a common name for all proteinaceous infectious particles?

During last years there were showed that other proteins can form amyloid fibrils which can seed native proteins making them change structure. Means these amyloid fibrils are proteinaceous infectious particles. Some of these proteins can even form different strains [6] So can we call such proteins prions? Or prion is only PrP and it is only one of amyloidogenic proteins like AmyloidBeta, IAPP, TTR which are also related to some diseases, or insulin, which can can behave similar to prions in certain conditions, but by now it was not involved in amyloid diseases?. V.S.

[7]: In its coinage, prion is PrPSC or beta amyloid. I hesitate to use "prion" in a positive context for normal function (if I can figure that out, if any), because of the coinage, so I might work it like this:
PrPSC: Beta Amyloid.
PrP: prion (I won't write TLAs unless I really can't think of something pronounsable).
PrP:C: normal prion.

Beta Amyloid is usually conjoined with plaque. 216.234.170.74 13:09, 31 July 2006 (UTC)

Beta-amyloid tends to refer to the peptide involved in alzheimers disease, and thus isn't really related to prions.


Other amyloid diseases are not infectious. A bit of amyloid from a someone with a non-prion disease cannot spark off the disease in a healthy person; a prion can - that is the key difference. There are other proteins than PrP that can form prions (i.e. that are truly infectious), but the only ones we know of are in yeast/fungi. You also need to bear in mind that 'amyloid' itself (beta-sheet protein fibrils) is not necessary for prion disease - it seems to build up as a kind of by-product. No-one knows what the actual infectious form looks like, or why other amyloid-forming proteins don't have this infectious form.

In my mind, the prion is the actual infectious form, which is not necessarily PrPSc (PrPSc is the name for the amyloid form of PrP). PrPC is the 'healthy' form of PrP, while PrP on its own refers to any structure of PrP. I would say that PrP is prion protein, while 'prion' alone means specifically the infectious form. Purple 13:03, 3 January 2007 (UTC)



Actually, the nomenclature of the various forms of PrP is still debated amongst prion researchers. For clarification, I've listed below just a few of the different names for some of the isoforms of PrP as outlined by Prof Charles Weissmann in his excellent review, The State of the Prion (Nature Reviews Microbiology 2, 861-871 (2004)).


PrPC

The physiologically occurring, mainly GPI-linked form of PrP, or prion protein, that can be glycosylated on one or both of two asparagine residues with a variety of glycans. As shown by NMR and X-ray crystallography, it is rich in alpha-helical structure and contains only a little beta-sheet structure.


PrPSc

An isoform of PrPC that is almost invariably detected in TSE-infected tissues and cells. It comprises a carboxy-proximal segment of about 140 residues that is resistant to defined conditions of PK treatment. The term PrPSc is used by some interchangeably with prion, a usage that should be avoided. PrPSc designates a structure, prion is a functional concept. The implication that a particular form of PrP is the only essential constituent of the prion remains to be proven.


PrP27-30

The PrP fragment remaining after controlled PK digestion of PrPSc. - Contrary to popular belief PrPsc is not entirely resistant to protease digestion, but instead has a protease-resistant core. (Pikzee)


PrP*

A hypothetical isoform of PrP that is the essential component of the TSE agent or prion.


Prnp

The gene encoding PrP


rPrP

Denotes recombinant PrP. When produced in Escherichia coli it lacks the GPI anchor and the glycan residues.

Pikzee 17:57, 21 March 2007 (UTC)

[edit] Fungal Prions 'Controversial'?

This statement is in the Fungal Prions section:

"This definition is controversial, since these proteins were not initially labelled as prions due to their infectivity, but because of their amyloid nature. It was not untill later that the potential for infectivity was discovered, and it is still not clear if infection occurs naturally."

Would you care to justify that? Long before they were determined to be prions, URE2 and PSI were studied because of their non-mendelian inheritance, which has been determined to be a consequence of their infectivity.

Morwan 01:05, 8 April 2006 (UTC)

[edit] Genetics or not?

brewhaha@ecn.ab.ca Two sentences near the start of this article hav TSEs as explicit subjects. I've set them off with . I also want to take out the bit about Lamarkian Evolution, because the example cited does not seem to reach DNA. It only goes as far as biological maladaptation. I'd like to believe in Lamarkian evolution, too, and I don't know of a mechanism for it that isn't mutagenic or that doesn't involve spermicidal or ovicidal effects.

I saw some passive voice in the article that isn't necessary, so I doubt that anyone has gone over this with Grammatik. I'm hoping that I can drop the required grade level with no significant change in meaning. Otherwise, there'll be too much shock at suddently being able to understand the article when someone gets to the part about dissent. I'm expecting complaints from Grammatik about the acronyms, so I'll use them once and thereafter try to spell things out. 216.234.170.83 08:52, 16 July 2006 (UTC)

[edit] Alzheimer's and prions

[8]: In Neuroinflammation in Alzheimer's disease and prion disease, I found support for both my speculation that prions relate to inflammation (immune system) and an addendum to a remark I made about Alzheimer's. As of yet, neither TSEs article nor prion article mention this neurodejenerativ disease. 216.234.170.74 12:46, 31 July 2006 (UTC)

BTW, I like Wiley's interface to their own abstracts more than NIH.

[edit] Section on Dissent

In paragraph fifteen of Brown's work, it explicitly says "There is currently no evidence that this manganese bound prion protein is infectious", so whoever was trying to say that Brown supports the protein-propagated cause of protease resistance was sorely misled.Brewhaha@edmc.net 20:33, 27 October 2006 (UTC)

[edit] Why does one of the paragraphs have a strikethrough through it?

Why is that so? Is it because the information is wrong, or is it someone's idea of a joke?

brewhaha@ecn.ab.ca: Maybe you should ask yourself why the whole section about "proposed mechanism of prion propagation" disappeared _without_ tags for warning. My version's going on bionet. 216.234.170.65 20:51, 16 July 2006 (UTC)

brewhaha@ecn.ab.ca: The paragraph you mention clearly relates to encephalopathies TSEs, but not diseased prions, which are not supposed to propagate with genetic reproduction. Even though they apparently do in the article about TSEs, the phenomenon is very rare. But really, when you talk about prions, you are invoking the topic of non-genetic propagation of biological characteristics.

I'm learning why copywriters normally get paid. As I activate and simplify the sentences to make this article more readable, some of them are actually getting redundant, repetitive and dogmatic, and I didn't like them to begin with, so I'm glad someone's watching, because on the first pass of my revision, I'm doing very little to the content. Just that part about TSEs and another bit about Lamarckian evolution. I'll let the change in style sink in for a while.

As for the bias in my section about dissent, no other explanation allows for this disease to survive incineration. And I think I will expose some bias under a veil when it comes to passive voice. 216.234.170.65 18:34, 16 July 2006 (UTC)

[edit] Kuru and Prions

I'm not sure if this is the right place to put my question, but I'm doing a research project on the Kuru disease and I'd like to know what exactly prions do that cause the brain to get "spongy".

Now, from reading the Prion article, I get that the PrP^Sc protein contains a lot more of the amino acid structure called "beta sheets" than the normal PrP^C proteins. Now assuming that HuPrP^Sc kuru protein is somewhat related to the PrP^Sc protein, these "beta sheets" allow the proteins to form insoluble fibrils called amyloid aggregations. How do these fibres cause problems? I'm only a grade 10 student, so I'd like a somewhat simplified answer so that I can understand what you are saying without having to research every word I don't understand. Your help is appreciated.

brewhaha@ecn.ab.ca: Amyloid aggregations have been found in Alzheimer's, too. Even with the revisions I'm submitting, this article has a grade 11-13 reading level according to mechanical scores. I've made my version just a bit easier to read than an insurance policy, and it's difficult for me to see if I'm incorporating all of the revisions I mean to, because Grammatik (my style checker) isn't compatible with the markup here. 216.234.170.65 20:21, 16 July 2006 (UTC)

[edit] Summary List

I notice that over time the article gradually seemed to concentrate more and more on BSE and its variants and leave out the other prion diseases. I think that it is useful to include them for the reader so they can see that this covers a wide range of diseases, and not just the BSE/TSE type. I have put the summary list at the bottom which existed in shortened form when the article was first started.--ReasonIsBest 17:15, 23 November 2006 (UTC)

Thanks, ReasonIsBest. I think that your edits are an improvement. – ClockworkSoul 17:17, 23 November 2006 (UTC)

[edit] Prion Genetics

Does anyone know if the prions that are considered human pathogens have ever been genetically mapped out and their protein functions understood? I am interested in those that affect the brain specifically

[edit] Why was this removed?

[edit] Therapeutic strategies

Recently Japanese scientists at the Obihiro University of Agriculture and Veterinary Medicine developed one of the first strategies to delaying the onset of disease. They found that sulfated glycosaminoglycans (GAGs) and sulfated glycans inhibit formation of protease resistant protein in cells and prolong the incubation time of scrapie-infected animals. Among the glycopyranosides and their polymers examined, monomeric 4-sulfo-N-acetyl-glucosamine (4SGN), and two glycopolymers, poly-4SGN and poly-6-sulfo-N-acetyl-glucosamine (poly-6SGN), inhibited PrPSc formation with 50% effective doses below 20 microg/ml, and their inhibitory effect became more evident with consecutive treatments. Structural comparisons suggested that a combination of an N-acetyl group at C-2 and an M-sulfate group at either O-4 or O-6 on glucopyranoside might be involved in the inhibition of PrPSc formation. Furthermore, polymeric but not monomeric 6SGN inhibited PrPSc formation, suggesting the importance of a polyvalent configuration in its effect. These results indicate that the synthetic sulfated glycosides are useful not only for the analysis of structure-activity relationship of GAGs but also for the development of therapeutics for prion diseases.[1]

Is it bad? --Filll 01:32, 30 November 2006 (UTC)

I didn't remove it, but I couldn't do much about the alphabet soup in it, either. Maybe it should be tersened a lot. Brewhaha@edmc.net 09:18, 30 November 2006 (UTC)

[edit] Exotic Ungulates

Can anyone state a good reason to separate one kind of hoofed animal from another? Brewhaha@edmc.net 09:18, 30 November 2006 (UTC) The section on exotic ungulates is currently red, because it's not in the wiki. Brewhaha@edmc.net 09:18, 30 November 2006 (UTC)

If you look in the scientific literature of the field, this is done commonly. For many TSEs, similar things are done. I am not sure if there are more subtle reasons, however.--Filll 14:15, 30 November 2006 (UTC)

[edit] Prion discovery attribution

  • I've removed three edits regarding the attribution of a "Dr. Deshpande at Cambridge University" as the discoverer of prions -- a PubMed search for "Deshpande AND prion" returns zero results. References? -- MarcoTolo 01:09, 22 January 2007 (UTC)

[edit] Spelling of Purdey

A minor change, but I corrected Mark Purdey's name from "Purdy". He was a member of the Purdey gunsmith family. Jonathan Silverlight 23:24, 22 January 2007 (UTC)

[edit] Are they disease agents

While prions exist there is still much debate whether they are the causal agents of disease. In a recent stucdy conducted by Johns Hopkins 12% or their researchers reported they show no evidence they do cause illness and suggest other germs may be at fault. Whether or not you agree with this, enough people disagree to at least present an opposing viewpoint in this article. If you can do so for HIV and vaccines you can do so for prions. —The preceding unsigned comment was added by 4.142.45.67 (talk • contribs) 2007-02-24T21:04:40 (UTC)

It it not clear (to me, a non-expert) exactly which viewpoint it is that you want presented. This depends on what one takes a "prion" to mean:
  • The introduction to the article suggests that something is a "prion" if and only if it is a proteinaceous substance that transmits a disease. Under this definition, however, it is meaningless to claim that "prions exist but do not cause disease".
  • Another possible definition would have a "prion" be any protein that has a configuration which is unusually resistant to denaturation/proteolysis.
  • A third possibility is that a "prion" is any protein with two possible configurations of which one catalyze the transformation of the other into itself. But the article seems to suggest that there is still doubt about whether this is actually true for PrP.
  • Finally "prion" might simply be an alternative name for the specific protein PrP and its homologues in different species.
I suspect that the lack of a clear definition in the article reflects a lack of scientific consensus about what the word ought to mean, but if so, that uncertainty itself deserves mention, I think. –Henning Makholm 22:15, 24 February 2007 (UTC)

[edit] Blood-brain barrier

Even if prions can resist digestion and make it into the bloodstream, how the heck do they get past the blood-brain barrier? ---Seven of Nine 19:17, 17 March 2007 (UTC)

Prions are believed to enter the brain through neuroinvasion (traveling along the nerves). After infectionof an animal/person, they enter the lymphoreticular system where they replicate (Kitamoto et al., 1991), particuarly in the spleen. They then travel from here into the sympathetic nervous system in a process which requires Follicular Dendritic Cells (FDCs) . It is not known how the prions move from FDCs into nerves as there is no physical contact between them. Once in the sympathetic nervous system, they can travel into the central nervous system and therefore, into the brain. Pikzee 17:06, 21 March 2007 (UTC)

[edit] Fatal Familial Insomnia

"... Fatal Familial Insomnia, a British disease that cultural preferences may cause."

This whole sentence not only sounds strange to me, I also couldn't find any proof for it. Even the Wikipedia article says that the first case was found in Italy and there are cases worldwide. Also, it is genetic, so which British cultural preference causes that?

[edit] prionic size and infectivity

Hai, work this intom the page: "NIAID Scientists Characterize the Most Infectious Prion Protein Particles" (2005). -lysdexia 04:24, 21 March 2007 (UTC)


Yes, it's quite important for the nature of the infectious agent - the identity of which is still debatable. Even in highly purified infectious fractions, only one in 105 PrPSc particles is infectious (Bolton and Bendheim, 1991). The most infectious prion protein particles have now been shown to be non-fibrillar particles containing 14 – 28 PrP molecules with infectivity significantly reduced in oligomers larger and smaller than this (Silveira et al., 2005). This is also in agreement with an emerging theme in other neurodegenerative disorders (such as Alzheimer's Disease) that the formation of amyloid may actually be a protective mechanism used by the cell to limit the ability of a toxic protein to trigger more conversion. Pikzee 18:13, 21 March 2007 (UTC)

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