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"Normal" Prions May Protect Myelin
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."
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.
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.
"Maybe this world is another planet's hell"
Aldous Huxley
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?
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.
#fuckbeta #iamslashdot #dicemustdie
Are there any extrernal factors that contribute to abnormal prions, such as pollutants, carcenogens, genes, etc?
oldhack: "Security is a waste of money until shit hits the fan. 5 minutes later, it becomes waste of money again. "
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.
...is you don't talk about Protect Myelin.
There's no -1 for "I don't get it."
As I read the article prions are misfolded prion proteins. 'Normal prions' sounds like an oxymoron.
"You must construct additional prions!"
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?
"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?
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?
I was thinking of a response more like:
We're all full up of idiocy here. Why don't you try next door?
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?
Ok, lots of partially correct information in the above posts
First, start with Wikipedia. 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, where it is passed on by cannibalistic consumption of human brains; Creutzfeldt–Jakob disease, 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 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. 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.