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Biotech Medicine

"Normal" Prions May Protect Myelin 81

Posted by kdawson
from the simple-fold-of-fate dept.
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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"Normal" Prions May Protect Myelin

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  • Oops... (Score:4, Interesting)

    by Monkeedude1212 (1560403) on Tuesday January 26, 2010 @04:58PM (#30910634) Journal

    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: (Score:3, Funny)

      by Cryacin (657549)

      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 (Score:3, Funny)

        by AlpineR (32307)

        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: (Score:2, Funny)

      by Anonymous Coward

      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: (Score:1, Funny)

      by Anonymous Coward

      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... (Score:5, Funny)

      by jollyreaper (513215) on Tuesday January 26, 2010 @05:23PM (#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: (Score:3, Funny)

      by Eudial (590661)

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

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

      • Re: (Score:2, Funny)

        by Anonymous Coward

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

    • by sjames (1099)

      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 :-)

    • by Shikaku (1129753) on Tuesday January 26, 2010 @05:43PM (#30911164)

      "You must construct additional prions!"

    • 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.

    • by creimer (824291)
      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.
    • 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.

    • by anexkahn (935249)
      me too....I was very confused as to how hanging out in a small concrete room would help with Myelin.
  • 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.
    • by 1800maxim (702377)
      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.
  • 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?

    • 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.
      • by ifwm (687373)

        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: (Score:3, Insightful)

      by Anonymous Coward

      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 genet

      • Re: (Score:2, Insightful)

        by IshmaelDS (981095)
        "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
      • "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 "unrelat

  • Prions (Score:4, Informative)

    by girlintraining (1395911) on Tuesday January 26, 2010 @05:03PM (#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.

    • I think I understand, but I also think a car analogy is in order.
      • Re:Prions (Score:4, Funny)

        by girlintraining (1395911) on Tuesday January 26, 2010 @05:25PM (#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 (Score:5, Informative)

      by khayman80 (824400) on Tuesday January 26, 2010 @05:51PM (#30911232) Homepage Journal

      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: (Score:2, Funny)

        Thank you for being awesome, khayman80. ^_^

        • by khayman80 (824400)

          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: (Score:2, Informative)

        by izomiac (815208)

        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 pr

    • 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

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

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

    • by ShaunC (203807)

      http://tolweb.org/Priapulida/2476

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

    • Re: (Score:2, Interesting)

      by vajrabum (688509)
      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: (Score:1, Interesting)

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

  • by Anonymous Coward on Tuesday January 26, 2010 @05:49PM (#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?

    • by dgatwood (11270) on Tuesday January 26, 2010 @06:08PM (#30911400) Journal

      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.

      • by thepotoo (829391)
        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?
        • by dgatwood (11270)

          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: (Score:3, Funny)

      by Chris Burke (6130)

      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!

    • 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!

    • by matt4077 (581118)
      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
    • Damn! Why did you post this as AC? I wanted to befriend you because of that comment!

  • 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 th

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