"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."

Comments

Prions

[girlintraining]

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

[khayman80]

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

[izomiac]

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

[girlintraining]

"I drank WHAT?" : Socrates

Actually, he mentioned his cock. ;)

Re:Summary, headline misleading

[dgatwood]

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:I read the summary and didn't understand any of

[JoshuaZ]

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?