Tuesday, February 15, 2011

prion-like cause for Lou Gehrig's disease?

From the blog Not Exactly Rocket Science:

Imagine a villain that corrupts those it touches. It can convert other individuals into twisted doppelgangers that eventually gather to form a destructive legion. This sounds like a character from any one of a hundred comic books, horror movies or science-fiction shows. But this antagonist is real, and it affects the brains of tens of thousands of people every year. It’s a mutant version of a protein called SOD1, and it causes amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease.

All proteins are long chains of amino acids that fold up in acts of molecular origami. This has to happen with great precision – if the protein ends up with the wrong shape, it won’t work properly. Some people have mutant versions of SOD1 that sometimes fold incorrectly. These deformed proteins have a habit of clumping together and – in mice at least – the symptoms of ALS get worse as the clumps get bigger. These misshapen versions of SOD1 probably cause around one or two in every hundred ALS cases.


Sounds like a prion, right? But it isn't. Prions are defined as being infectious to other people, and extremely hardy and difficult to kill. On the other hand, these SOD-1 proteins do not seem to survive well outside the cell, and do not appear to kill their "host" cells. This may ultimately lead to a treatment that targets the mutant proteins as they spread in the spaces between cells.

But wait, there's more...

ALS and prion diseases are just some of the many brain diseases that are caused by misshapen proteins that gather together in clumps. These doppelgangers are also implicated in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and more. Bertolotti says that her study is the first to conclusively show that a protein other than prions can “infect” normal proteins with their twisted shapes.

The original journal article can be found here: PNAS article

The blog post is here: Not Exactly Rocket Science

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