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"Normal" Prions May Protect Myelin

kdawson posted more than 4 years ago | from the simple-fold-of-fate dept.

Biotech 81

thomst writes "Nature Neuroscience just published an online article about the function of 'normal' prions in protecting myelin, the substance that sheathes and protects sensory and motor nerves. The international study (which has 11 authors) concluded that 'normal' (i.e., not mis-folded) prions may form a protective coat around myelin. The researchers found that Prnp -/- mice (mice with the gene for prions knocked out) consistently developed progressive demyelination, inevitably leading to persistent polyneuropathy by 60 weeks of age. Their data suggest that damage to myelin sheaths cause normal prions to cleave, and the resulting prion fragments activate Schwann cells, which are known to play a part in myelin repair. This research might eventually lead to possible treatments for progressive polyneuropathies in humans, including those mediated by Creutzfeldt-Jakob disease, multiple sclerosis, Alzheimer's, and even diabetes."

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Oops... (3, Interesting)

Monkeedude1212 (1560403) | more than 4 years ago | (#30910634)

I kept reading "Prisons" instead of Prions and was dumbfounded beyond belief.

I looked away from my screen for a minute imagining the possibilities. Then I looked back, noticed my mistake, and felt like an idiot.

And thats why I'm posting; I'd like to share my idiocy with you.

Re:Oops... (2, Funny)

Cryacin (657549) | more than 4 years ago | (#30910830)

And thats why I'm posting; I'd like to share my idiocy with you.

No worries my good man! This is slashdot. You are in good company.

Idiocy (2, Funny)

AlpineR (32307) | more than 4 years ago | (#30912598)

I was thinking of a response more like:

And thats why I'm posting; I'd like to share my idiocy with you.

We're all full up of idiocy here. Why don't you try next door?

Re:Idiocy (0)

Anonymous Coward | more than 4 years ago | (#30925156)

But I just CAME from Digg, they were full up too!

Re:Oops... (2, Funny)

Anonymous Coward | more than 4 years ago | (#30910832)

I did the same thing. I started reading the summary and got to the part about the mice and said to myself, "What are the mice doing in prison?" Doh!

Re:Oops... (1, Funny)

Anonymous Coward | more than 4 years ago | (#30910836)

I was anticipating a myelin's law, kind of like megan's law, since prions arent doing a good job protecting the public.

Re:Oops... (4, Funny)

jollyreaper (513215) | more than 4 years ago | (#30910940)

I kept reading "Prisons" instead of Prions and was dumbfounded beyond belief.

I looked away from my screen for a minute imagining the possibilities. Then I looked back, noticed my mistake, and felt like an idiot.

And thats why I'm posting; I'd like to share my idiocy with you.

And I'm thinking "I know hybrid cars are supposed to be good for the environment but aren't they overselling it a bit much? And who makes the Prion anyway, is that Dodge or Toyota?"

Re:Oops... (2, Funny)

Eudial (590661) | more than 4 years ago | (#30910970)

I kept reading "Prisons" instead of Prions and was dumbfounded beyond belief.

News at 10: D&D harmful to Myelin [slashdot.org] .

Re:Oops... (2, Funny)

Anonymous Coward | more than 4 years ago | (#30911126)

He misread it as "prisons" not "psions" ...

Re:Oops... (1)

sjames (1099) | more than 4 years ago | (#30911140)

And thats why I'm posting; I'd like to share my idiocy with you.

That's the net's primary function! Thanks for doing your part :-)

Not as bad as thinking... (3, Funny)

Shikaku (1129753) | more than 4 years ago | (#30911164)

"You must construct additional prions!"

Re:Not as bad as thinking... (1)

KingPin27 (1290730) | more than 4 years ago | (#30911454)

"You must construct additional prions!"

"you require more minerals"

Re:Not as bad as thinking... (1)

Gerafix (1028986) | more than 4 years ago | (#30921436)

Of course the American politicians received the message as, "You must construct additional prisons!"

Re:Oops... (1)

interkin3tic (1469267) | more than 4 years ago | (#30911360)

And thats why I'm posting; I'd like to share my idiocy with you.

I had that problem before I went to prison. Figured out it had something to do with my elin.

It was probably my puns that sent me to prison in the first place.

Re:Oops... (1)

creimer (824291) | more than 4 years ago | (#30911440)

I read "'Normal' Peons May Protect Masters" as the headline. WTF? If I recall my Warcraft 2 days, even "abbey-normal" peons did a poor job of protecting their masters. However, they were wonderful at clearing the forest of an entire continent if you let the game run overnight.

Re:Oops... (1)

Antidamage (1506489) | more than 4 years ago | (#30911498)

You're not too off the mark there, Freud. Speaking as someone enjoying demyelination on two fronts (blindness, neuropathy, separate reasons) it is a bit of a prison.

Re:Oops... (1)

anexkahn (935249) | more than 4 years ago | (#30912496)

me too....I was very confused as to how hanging out in a small concrete room would help with Myelin.

Re:Oops... (0)

Anonymous Coward | more than 4 years ago | (#30912922)

wow, i cant belive it, i did the same thing and did an "wtf" and called a friend over to read this. Who corrected me.

dumb dumb dumb

Re:Oops... (0)

Anonymous Coward | more than 4 years ago | (#30918024)

And I felt the same idiocy too, I know what Myelin is and what a prion is and what a cleaving is and still read it as normal "prisons" :(... are there abnormal prisons anyways?

An abnormal prison can be that where the inmates graduate and they are fully rehabilitated, institutionalized and their criminal personality has been totally neutralized not that they go out of there with the hell-bent determination of coming back at the rats who ushered them in but with the hell-bent determination of going out of there to love the world and give it a big hug...

Any treatment options are good (1)

Meshach (578918) | more than 4 years ago | (#30910656)

Since this study suggests treatments for diseases which presently have very few treatments (MS, Alzheimer's) this is very good news. Hopefully it will translate into new treatments someday.

Re:Any treatment options are good (0)

Anonymous Coward | more than 4 years ago | (#30911662)

Hopefully it will translate into new treatments *soon*. I'm sure there will be plenty of new treatments someday, but that's small consolation for the millions of people living with this now (and their families).

Re:Any treatment options are good (1)

1800maxim (702377) | more than 4 years ago | (#30917426)

It is possible to rebuild myelin sheath with essential fat oils (flax seed oil) and superfoods such as spirulina. I know because I'm a living example of it. But that was due to excessive caffeine thinning out my myelin. So, reduce caffeine too.

Aren't prions also responsbile for disease? (2, Interesting)

ifwm (687373) | more than 4 years ago | (#30910692)

So, this seems to indicate that some other disease causes malfunctioning prions, which result in a new disease such as CJS.

Does that mean something like a family history of MS for instance, which results partially from myelin damage, is an indicator for CJS?

Re:Aren't prions also responsbile for disease? (1)

ArbitraryDescriptor (1257752) | more than 4 years ago | (#30910966)

Do you mean CJD? If MS suggests a lack of prions you have to ask if they are missing because they are misfolded, or because your body did not produce them in sufficient numbers. A failure to produce prions should technically protect you from CJD as they can't run amok in your brain if they aren't there.

Re:Aren't prions also responsbile for disease? (1)

ifwm (687373) | more than 4 years ago | (#30911318)

No, I meant "creutzfeldt jakob syndrome" which is a perfectly acceptable name for the disorder.

Please stop trying to correct things if you don't know what you're talking about.

Re:Aren't prions also responsbile for disease? (1)

csartanis (863147) | more than 4 years ago | (#30917914)

Google and Wikipedia tell me that you're wrong, not him. You shouldn't criticize people when it's going to make you look like the dumbass.

Creutzfeldt–Jakob disease [wikipedia.org]

Re:Aren't prions also responsbile for disease? (3, Insightful)

Anonymous Coward | more than 4 years ago | (#30910982)

A prion is a protein that modifies other proteins to take on its shape, creating a chain reaction that converts all/most of the normal form into the prion form. Usually, the prion is a malformed protein that has an important function in its normal role. Malformed proteins are not at all uncommon (in fact a significant portion of cellular activity results in mistakes!) but ones that are contagious in this way can persist if they get transferred to other organisms. Generally this involves cannibalism or genetics, so Mad Cow Disease and other transmissible spongiform encephalopathies such as CJS are ultimately self-limiting.

However, prions are not, in principle, limited to myelin, and there are a lot of things that can go wrong in myelin sheaths. Your example, multiple sclerosis, actually results from the immune system attacking myelin, which is an unrelated problem. The immune system looks for markers to know what belongs and what doesn't, so it's probable that MS is normally caused by damage to the genes that are responsible for the creation of these markers in the first place.

It is conceivable that a mutant or misfolded protein could actively damage the markers, but the likelihood of this being a major cause is pretty small, simply because, from what we know, there are so many things that are more likely to go wrong.

Re:Aren't prions also responsbile for disease? (2, Insightful)

IshmaelDS (981095) | more than 4 years ago | (#30911312)

"Your example, multiple sclerosis, actually results from the immune system attacking myelin, which is an unrelated problem. The immune system looks for markers to know what belongs and what doesn't, so it's probable that MS is normally caused by damage to the genes that are responsible for the creation of these markers in the first place." While this is true this could lead to a treatment that could possibly regrow/repair the Myelin sheath around the nerves in those that have MS, one of the big problems in this disease is that as the immune system attacks it causes scars to form in the myelin which stay, and then on further attacks get re-aggravated, while this treatment may not cure MS it may cut down on the relapses and prevent disability's due to previous attacks.

Re:Aren't prions also responsbile for disease? (1)

statusbar (314703) | more than 4 years ago | (#30911796)

MS may be different in some people:

http://www.cbc.ca/health/story/2009/11/23/multiple-sclerosis-zamboni-ccsvi.html [www.cbc.ca]

--jeffk++

Re:Aren't prions also responsbile for disease? (1)

IshmaelDS (981095) | more than 4 years ago | (#30927898)

Awesome, thanks for the link, I must have missed that story. My wife has MS and will be very interested in reading about that. If I could I would mod you up as that should be at the least 3 insightfull

Re:Aren't prions also responsbile for disease? (1)

kcitren (72383) | more than 4 years ago | (#30913920)

The jury still isn't out over whether MS is a purely auto-immune disease.

No, I'm sorry, you can't just claim this (2, Interesting)

ifwm (687373) | more than 4 years ago | (#30911388)

"However, prions are not, in principle, limited to myelin, and there are a lot of things that can go wrong in myelin sheaths. Your example, multiple sclerosis, actually results from the immune system attacking myelin, which is an unrelated problem."

How do you know this? According to the article, they may very well be related, for example, when the immune system attacks the myelin, the byproduct of the breakdown could be malfunctioning prions.

I don't see anything that proves in any way that they're "unrelated" as you claim, and in fact, current theories seem to indicate you are wrong, so why aren't you?

Re:Aren't prions also responsbile for disease? (0)

Anonymous Coward | more than 4 years ago | (#30911040)

Does that mean something like a family history of MS for instance, which results partially from myelin damage, is an indicator for CJS?

No, not the way I read the summary.

A genetic predisposition for MS could possibly result from a miscoded gene for normal prion production, leading to lack of myelin protection, leading to polyneuropathy.
And presence of CJS results from misfolded prions, which also leads to a lack of myelin protection, leading to polyneuropathy.

But no connection between predisposition for MS and CJS is drawn so far.

Prions (4, Informative)

girlintraining (1395911) | more than 4 years ago | (#30910712)

The problem with prions, as I understand it, is that they can't be targeted by the autoimmune system because they can't be bonded to; And that is because of the blood-brain barrier. Normal prions are folded proteins that self-terminate. That is, they end after a certain number of repeats. But abnormal ones don't ever stop growing -- and they occasionally break apart, but they keep folding forever. It's like trash that never biodegrades, in your body, clogging up the space between nerve endings until nothing gets through. That's not a technically accurate description, but it's a good way to view the problem.

Re:Prions (1)

lastomega7 (1060398) | more than 4 years ago | (#30910776)

I think I understand, but I also think a car analogy is in order.

Re:Prions (4, Funny)

girlintraining (1395911) | more than 4 years ago | (#30910976)

I think I understand, but I also think a car analogy is in order.

Fine. *mutter, mutter* Your car is just a metaphor for a folding protein called a prion. Except your car isn't a car, but a robot. We'll call it a transformer. Now there are good transformers, and Decepti--I mean, bad robots. The bad robots are bad because they just don't know when to stop. And they want to take over everything using a device called the AllSpark. The AllSpark is the source of ultimate power for the robots good and bad. Except the AllSpark is really nucleic acid. The only way to beat the Deceptic--I mean, bad prions, is to destroy the AllSp--er, nucleic acid. But that would be bad, because without the nucleic acid, none of the cars would run, nobody would get anywhere, and then anarchy would result and the world would end.

Re:Prions (2, Funny)

dreamchaser (49529) | more than 4 years ago | (#30911642)

I think I love you in a platonic sort of way.

Re:Prions (2, Insightful)

girlintraining (1395911) | more than 4 years ago | (#30911812)

I think I love you in a platonic sort of way.

Well, as long as it stays platonic I won't send you the way of Socrates.

Re:Prions (1)

dreamchaser (49529) | more than 4 years ago | (#30911992)

You do know what his last words were, right?

"I drank WHAT?" : Socrates

Re:Prions (2, Informative)

girlintraining (1395911) | more than 4 years ago | (#30912034)

"I drank WHAT?" : Socrates

Actually, he mentioned his cock. ;)

Re:Prions (0)

Anonymous Coward | more than 4 years ago | (#30913136)

Somehow I don't think "Hrmm, tastes like chicken" equates to the mentioning of one's cock.

Re:Prions (0)

Anonymous Coward | more than 4 years ago | (#30911042)

The prion is like a used car, and the RIAA wants to sue you because someone ate it and contracted kuru without paying for it. Wait, I fucked that up somewhere.

Parent is a racist, mod down forever (-1, Troll)

Anonymous Coward | more than 4 years ago | (#30910924)

I'm surprised you're still posting after that racist tirade about Haiti you posted.

http://slashdot.org/comments.pl?sid=1521586&cid=30867598 [slashdot.org]

Really, you're disgusting, and I intend to make sure you're outed as a racist every time I see you.

Re:Parent is a racist, mod down forever (-1, Offtopic)

girlintraining (1395911) | more than 4 years ago | (#30911024)

I'm surprised you're still posting after that racist tirade about Haiti you posted.

That word, I do not think it means what you think it means. Saying that humanity as a whole is filled with dumb, irrational, self-centered individuals isn't racist.

Really, you're disgusting, and I intend to make sure you're outed as a racist every time I see you.

Well, if you're going to "out" me, could you at least do me (and everyone else) a favor and link to a post that actually contains a racist comment?

Thanks, timmarhy. ;)

Re:Parent is a racist, mod down forever (-1, Offtopic)

Cryacin (657549) | more than 4 years ago | (#30911026)

Have I missed something? I looked at your link Mr. AC, and I see no racist remarks? I see cultural observations, but if you're going to pull the racist card, I'd think that the other party involved was closer to being racist than girlintraining.

Oh wait, you didn't expect anyone to read the comment and just go by your accusation? Right. Everything clear now.

Re:Parent is a racist, mod down forever (-1)

Anonymous Coward | more than 4 years ago | (#30911094)

Oh wait, you didn't expect anyone to read the comment and just go by your accusation? Right. Everything clear now.

Yeah, but the mods are still going to come and nuke the girlintraining's karma for replying to it, so it's a very successful troll. The mods fall for that trick every time.

Re:Parent is a racist, mod down forever (-1)

Anonymous Coward | more than 4 years ago | (#30911084)

I think you should reread girlintraining's posts about Haiti. I don't think that those posts are racist in the slightest. In fact, she seems to be making the exact opposite point that people from any culture could act like that, if the society is stressed enough.

If you really think that she wrote something so horrible that it has no place in civilized discourse, quote it, because I don't see it.

Re:Prions (5, Informative)

khayman80 (824400) | more than 4 years ago | (#30911232)

The problem with prions, as I understand it, is that they can't be targeted by the autoimmune system because they can't be bonded to; And that is because of the blood-brain barrier.

Prions are dangerous mainly because proteins are more stable than nucleic acids, so sterilization techniques that are adequate against viruses and bacteria aren't effective against prion-based diseases like BSE and CJD.

Normal prions are folded proteins that self-terminate. That is, they end after a certain number of repeats. But abnormal ones don't ever stop growing -- and they occasionally break apart, but they keep folding forever.

Prions are proteins that have mis-folded. They stop folding on the same microsecond timescale as normal proteins, but most develop "amyloid folds" that (as you say) causes them to build up like trash in the body.

Prions certainly stop growing. Also, a big problem is that they form structures that are very stable. You seem to be describing cancer, which is effectively immortal, lacks the usual constraints on mitosis frequency, and breaks apart (metastasizes) to spread throughout the body.

A prion's actual method of infection is that the mis-folded protein induces other correctly-folded proteins in its vicinity to change to the mis-folded state.

Re:Prions (2, Funny)

girlintraining (1395911) | more than 4 years ago | (#30911372)

Thank you for being awesome, khayman80. ^_^

Re:Prions (1)

khayman80 (824400) | more than 4 years ago | (#30911450)

I try. ;)

For what it's worth, your post should be modded interesting at the very least, if only to annoy that AC stalker you seem to have acquired.

Re:Prions (-1, Offtopic)

girlintraining (1395911) | more than 4 years ago | (#30911734)

For what it's worth, your post should be modded interesting at the very least, if only to annoy that AC stalker you seem to have acquired.

I'll depart from my busy schedule of lesbianism and witchcraft to field this one. ;)

He's part of a growing fan club of emotionally under-developed males unaccustomed to having girls in their internet man cave, let alone a gay one. The community outwardly states they aren't sexist. They're smart, well-educated, (generally) white men, and so overt displays of sexism are met with open contempt. This is why they moderate most of the posts by "the fan club" down. But then they moderate my posts down because I attract them. They think it's at least partly my fault because my presence provokes them. And in that little microcosm of human behavior, is the reason sexism, racism, homophobia, and most human prejudice is allowed to endure.

Re:Prions (0)

Anonymous Coward | more than 4 years ago | (#30912706)

Oh you're GAY! I figured you were a Transexual or into BDSM or something.

But Lesbian! Pics or it didn't happen! kthxbye!

It's like thousands of nerds cried out in agony and were suddenly silenced.

Re:Prions (0)

Anonymous Coward | more than 4 years ago | (#30915698)

Don't worry, GinT. You have a real fan club here, too, friend.

Re:Prions (2, Informative)

izomiac (815208) | more than 4 years ago | (#30911910)

Prions are dangerous mainly because proteins are more stable than nucleic acids, so sterilization techniques that are adequate against viruses and bacteria aren't effective against prion-based diseases like BSE and CJD.

Minor correction: Proteins, in general aren't particularly stable. Some are, but others aren't. Your DNA, depending on the G-C content, will melt at ~140 F, whereas a bad fever will start to denature proteins at ~108 F. Even PrP-C (Prion Protein - normal, endogenous form) isn't particularly stable. The PrP-SC (disease form, e.g. Scrapie, Mad Cow, or CJD) converts some of PrP-C's alpha helices into more compacted beta-pleated sheets, which make the protein very resistant to heat and the body's natural proteases. It also makes it aggregate into amyloid deposits in the brain, which are even more stable. These deposits create a "sponge-like" appearance, hence why the diseases are called "spongiform encephalopathy".

There are a great many methods that can be uses to kill something with DNA (parasites, bacteria, viruses, etc.), such as UV light, moist heat, and various chemicals. The PrP-SC can "survive" normal autoclave temperatures that kill almost everything else. Since they lack DNA, UV light and DNA-degrading chemicals aren't going to do much to them. And because they're a single protein it's very difficult to develop a drug that can target them specifically, degrade them, and not affect the normal PrP-C. The body's antibodies might work, but they stay out of the brain due to the blood-brain barrier (also why meningitis can easily kill you), although this effect is reduced if inflammation occurs.

One tragedy of CJD is that PrP-SC amyloid deposits stay in the brain, so the only way to be sure of the diagnosis of CJD is by brain biopsy. Therefore, it's commonly misdiagnosed, neurosurgery is performed on that patient, and PrP-SC gets on the surgeon's instruments. Since standard sterilization techniques are insufficient, it's often spread to other patients before being noticed.

Re:Prions (1)

khayman80 (824400) | more than 4 years ago | (#30911966)

Thanks for the correction and all the additional info.

Re:Prions (1)

lazy genes (741633) | more than 4 years ago | (#30927446)

Can you comment on the role that glycine and proline play in the folding of this beta strand.

Re:Prions (1)

interkin3tic (1469267) | more than 4 years ago | (#30911504)

they can't be targeted by the autoimmune system because they can't be bonded to; And that is because of the blood-brain barrier

I'd also guess without doing any reading on the subject that being inside the cell further prevents this. If a virus is inside a cell, that will ideally (for the cell) trigger cell suicide. If that doesn't happen or the virus blocks it. Some (most?) cells move bits of protiens out to their surface after they've digested them as part of normal cell function. If a bit of a viral protein does this, immune cells can recognize it and tell the cell to kill itself or can signal other cells to kill the infected cell. Since the prion though is a protein that is normal, the digested bits I would guess don't trigger that response, the immune cell sees the fragment and doesn't think anything is wrong.

Normal prions are folded proteins that self-terminate. That is, they end after a certain number of repeats. But abnormal ones don't ever stop growing -- and they occasionally break apart, but they keep folding forever.

Not sure what is meant by self terminating vs repeats, sounds like you're talking about translation, that prions don't stop synthesizing an amino acid chain. This page [rcn.com] suggests that the proteins are made normally, its just that the misfolded proteins bend the normal ones out of shape. These proteins are insoluable, they form clumps (aggregates) inside the cell that are resistant to digestion, so the cell can't get rid of them. It does say though that no one had shown that was the cause rather than just one effect.

Re:Prions (1)

poopdeville (841677) | more than 4 years ago | (#30913186)

Why was this modded informative? It's all absolutely wrong.

What causes abnormal prions? (1)

uslurper (459546) | more than 4 years ago | (#30910744)

Are there any extrernal factors that contribute to abnormal prions, such as pollutants, carcenogens, genes, etc?

Re:What causes abnormal prions? (1)

ShaunC (203807) | more than 4 years ago | (#30910844)

http://tolweb.org/Priapulida/2476

Yes, they're called priapulidae [tolweb.org] .

Re:What causes abnormal prions? (2, Interesting)

vajrabum (688509) | more than 4 years ago | (#30910952)

Mad cow disease or creutzfeldt jakob disease and kuru or laughing sickiness are prion diseases. Both are caused by eating infected nervous tissue or brains. Apparently prion disease is caused by eating misfolded prions. These misfolded prions apparently get into your nervous systems cause the normal prions in your nervous system to misfold as well.

Re:What causes abnormal prions? (2, Interesting)

PrimordialSoup (1065284) | more than 4 years ago | (#30911390)

The Cause is unknown..infact we arent even sure of the functions of normal prion proteins, this paper gives them a function of being Myelin protective...

I read the summary and didn't understand any of it (0)

Anonymous Coward | more than 4 years ago | (#30910878)

I read the summary and didn't understand any of it.

These scientists need to learn to use normal language and explain things so common rocket scientists can understand them.

Re:I read the summary and didn't understand any of (2, Informative)

JoshuaZ (1134087) | more than 4 years ago | (#30912004)

Ok. Prions are proteins that are misfolded. Proteins are special molecules made out of chains amino acids which then fold into useful shapes. Most of the biochemistry in your body has proteins involved in some way. Unfortunately, proteins can misfold. Worse, certain classes of misfolded proteins, called prions, can cause other proteins to misfold in the same way. Once proteins are misfolded they get in the way and muck things up. Some diseases like mad cow diseases are caused by prion infection. Another example is kuru, which is a disease that has been believed to be transmitted through ritual canibalism of dead kin in Papua New Guinea. This article suggests that the proteins that commonly form certain types of bad proteins are in their good (not misfolded state) responsible for helping protect the myelin sheath, which is a sheathe around part of your neurons that they get very unhappy when they don't have it. This discovery has potential implications both for treating diseases that involve problems in the myelin sheath, such as multiple scherlosis which is caused by your own immune system mistakenly attacking the myelin sheath. This discovery may also help us treat prion caused diseases. Is that summary more helpful?

The first rule of Protect Myelin... (1)

MrEricSir (398214) | more than 4 years ago | (#30910890)

...is you don't talk about Protect Myelin.

prion proteins != prions (0)

Anonymous Coward | more than 4 years ago | (#30910926)

As I read the article prions are misfolded prion proteins. 'Normal prions' sounds like an oxymoron.

Re:prion proteins != prions (1)

wizardforce (1005805) | more than 4 years ago | (#30911150)

Not all prions are bad [sciencenews.org] . Yeast for example have several prions that serve essential functions in the cell. The problem with human prions is that they are defective, they form plaques and damage cells while converting healthy proteins to defective ones.

Re:prion proteins != prions (2, Insightful)

MachDelta (704883) | more than 4 years ago | (#30911226)

The sticking point here is that prion is defined as an infectious agent. Saying "normal prion" or "non-infectious prion" is like saying "non-explosive bomb". The adjective contradicts the nouns definition. What they're actually referring to are proteins (like PrP) which are the precursor to a prion (they can change into one). Apparently those proteins have some other uses too, which makes sense seeing as how evolution has a tendency to discard things that aren't in use.

Re:prion proteins != prions (0)

Anonymous Coward | more than 4 years ago | (#30911334)

'Normal' prion proteins are not contagious. Prions, on the contrary, are. This holds true weather or not the prions have beneficial effect.

From the article: "Prions cause transmissible neurodegenerative diseases associated with accumulation of PrP(Sc), a misfolded and aggregated form of the cellular prion protein PrP(C)".

Summary, headline misleading (5, Interesting)

Anonymous Coward | more than 4 years ago | (#30911212)

First, some background. Most people won't know what a prion is, so I'll explain with a bit of a computer analogy.

Most proteins are like binaries, being executed by the universe. If you put another molecule next to it (usually called a 'substrate') then it will do things to that molecule, by changing its shape and moving its charge around. Enzymes are proteins that return to their original shape afterward. There are also some relatively inert proteins that don't change shape or do anything; they're just for structural purposes.

The mechanics of the cell are very flaky, however. In a computer, we can be sure that when we copy a program from disk (DNA) into memory (polypeptides, an actual molecule) and run it, we'll get an exact copy. In molecular biology, though, all of these processes are imperfect: sometimes we copy the wrong data into the data bus (transcription errors), sometimes we write the wrong thing into RAM (translation errors), and sometimes, since these are 3D structures that need to fold into a proper shape to work, we actually rearrange the bytes that get loaded into memory (there are lots of bits that say 'insert tab A into slot B', but they work off electrical charges). This is called misfolding, reasonably enough. Most of the time the cell can recognise a malformed protein and marks it for deletion with a molecule called ubiquitin. (It then gets sent to the bit bucket.) To make matters worse, proteins can get old and misfold on their own (this usually calls for another round of ubiquitin if the protein doesn't break down totally)

A prion is a very specific class of misfolded protein, which appears sufficiently normal to the cell that it can't decompose it, lives in the brain where the body's immune system can't obliterate it, and, most importantly, if it collides with other proteins of what it was supposed to look like, it will turn them into prions as well, somewhat like vampires, zombies, or your classic EXE-modifying computer virus. The effect is that the prion spreads exponentially, screwing up the machinery of the cell.

Now, a protein has to be really complex for this to be possible. Some proteins are really simple, like the humble microtubule, which just provides a conduit, and some are incredibly complex, like DNA polymerase, which reads the nucleotides on DNA and makes a duplicate. These proteins are usually highly conserved (that is, they look very similar in many species, because if they break, the organism dies, and evolution hits a dead end), and very, very important. As a result, when a prion forms, it comes at a great cost to the overall health of the organism. Worse, it's transmissible (though usually only by cannibalism, which is kind of funny in a scary sort of way.)

So, after all that, what am I complaining about? Well, the headline makes it sound like we've discovered a case of stable self-modifying code, but we haven't. The article just talks about a protein, PrP^C, which is known to cause a prion problem when broken. It's named "axonal prion protein" because, until this study was conducted, that's all we knew about it: if it broke, it was bad. Similarly, there are a bunch of genes called "oncogenes" because they cause cancer if they break, but they're actually really important; removing them generally prevents cell division completely. There is no such thing as a "normal" prion, at least not one introduced by this article. It just turns into a prion if it breaks.

But hey, I'm only an undergrad; what do I know?

Re:Summary, headline misleading (3, Informative)

dgatwood (11270) | more than 4 years ago | (#30911400)

The immune system can obliterate things in the brain--meningitis being the obvious example. In fact, there are some experimental tests being done that use the immune system to kill cancer cells in the brain. The immune system just doesn't have a mechanism for dealing with prions, and there's some possibility that it may be complicit in spreading the problem. And there have been some partially successful immunotherapy experiments on prions in mice, too.

Otherwise, yes, that's pretty close.

Re:Summary, headline misleading (1)

thepotoo (829391) | more than 4 years ago | (#30916378)

I thought part of meningitis was often the breakdown of the blood brain barrier, thus allowing the immune system in. If the blood brain barrier is still active (as it should be in prion diseases, unless they specifically target astrocytes), shouldn't it be impossible for the immune system to enter the brain?

Re:Summary, headline misleading (1)

dgatwood (11270) | more than 4 years ago | (#30926694)

Depends on how narrowly you define the immune system. There are microglial cells [wikipedia.org] that operate within the brain and spinal cord that behave like macrophages, except that they are in the brain and spinal cord. Presumably any immunotherapy would be training those cells, not mucking with T cells or B cells. I'm just guessing, though. Or they might be triggering inflammation sufficient to allow other immune cells through. Not sure.

Re:Summary, headline misleading (1)

thepotoo (829391) | more than 4 years ago | (#30938664)

That makes sense. Thanks for the reply.

Re:Summary, headline misleading (2, Funny)

Chris Burke (6130) | more than 4 years ago | (#30911422)

Worse, it's transmissible (though usually only by cannibalism, which is kind of funny in a scary sort of way.)

I think it's hilarious in my black-humor way.

It turns out you really can eat the brain of your enemy to gain their power... but only if their "power" was a debilitating brain disease!

Re:Summary, headline misleading (0)

Anonymous Coward | more than 4 years ago | (#30911604)

Don't expect the editor to actually grasp the article or for that matter update factual errors.

Re:Summary, headline misleading (1)

failedlogic (627314) | more than 4 years ago | (#30913368)

Brilliant. Yours is probably the clearest explanation of a prion I have read. I was confused on some of the points and this clears it up for me. Thanks once again!

Re:Summary, headline misleading (1)

matt4077 (581118) | more than 4 years ago | (#30914812)

Small correction: No mutation is needed for misfolding. It's just a single AA chain that can fold in the normal way, or a pathological way. The pathological form is actually able to tranform healthy ones to the path. form

Re:Summary, headline misleading (1)

Hurricane78 (562437) | more than 4 years ago | (#30948178)

Damn! Why did you post this as AC? I wanted to befriend you because of that comment!

what does this mean? (0)

Anonymous Coward | more than 4 years ago | (#30915234)

as someone who is diagnosed with Charcot Marie Tooth disease, advances in this field have the potential to greatly enhance my life, my siblings lives, and the lives of any children we have. Can some please explain, in plain english, what this means? what benefits and advances does this bring to the treatment of conditions that involve the deteriation of myelin?

Basic Prion Biology (1)

listentoreason (1726940) | more than 4 years ago | (#30916060)

Ok, lots of partially correct information in the above posts

First, start with Wikipedia [wikipedia.org] . A prion is a self-replicating protein. It represents a misfolded form of a protein normally produced by the host organism. This misfolded form has the capability to 'template' its normally folded protein cousins into prions; this appears to happen when a prion binds /aggregates to the normal form, inducing a stable conformational change of the normal form to the prion state. Prions do not have to be in the brain, but the nastiest form (known) in humans causes brain degeneration in three known diseases - Kuru [wikipedia.org] , where it is passed on by cannibalistic consumption of human brains; Creutzfeldt–Jakob disease [wikipedia.org] , which occurs spontaneously very rarely, more often due to a pre-existing mutation in the PRNP gene that greatly increases the likelihood of a random misfolding event, and BSE [wikipedia.org] where a cow prion is transmitted to humans, generally after eating meat contaminated with central nervous tissue from the cow.

Prions also exist in yeast [wikipedia.org] . There are several characterized variants, some of which are beneficial to the "infected" host, such as "[allowing] growth on poor nitrogen sources" (see the table in the link). Yeast prions represent an important model in studying prion biology.

The blood-brain barrier does prevent antibodies from crossing into the brain. Otherwise, there would be nothing to prevent the body from recognizing prions as "wrong" - while the prion shares the same secondary (linear) structure as the normal protein, the tertiary (3-D) structure is distinct. Antibodies recognize tertiary sub-structures, so if they had access to circulating prions they could bind to them. Some comments above on prion stability; some prions do in fact appear to be highly stable (most researchers accept that BSE can still be transmitted in cooked meat). This may in part be due to the fact that the prion form in that disease (and CJD / Kuru - same protein) forms large aggregates. I don't know that it's reasonable to say that prions are somehow generally more stable than DNA, though. Proteases (proteins that cleave other proteins) have the potential to destroy prions, as do denaturing conditions (those that cause the unfolding of the tertiary structure to secondary, linear form) - yeast can be "cured" of most prions by treating with urea, which increases the unfolding rate and allows refolding to the 'normal' form.

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