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How disordered proteins spread from cell to cell, potentially spreading disease
Date:2/18/2011

ideal for a lot of the standard communication that happens within a cell for its normal functioning, Kopito said.

But if some of our proteins are always disordered, how do our cells tell which proteins need to be properly folded, and which don't? "It's a big mystery," said Kopito, and one that he's studying. This question has implications for how people develop neurodegenerative diseases, all of which appear to be age-related.

Huntington's disease is caused by a specific mutated protein. But the body makes this mutant protein all your life, so why do you get the disease in later adulthood? Kopito said it's because the body's protective mechanisms stop doing their job as we get older. He said his lab hopes to determine what these mechanisms are.

A bad influence

But it's clear what happens when these mechanisms stop working misfolded proteins start recruiting normal versions of the same protein and form large aggregations. The presence of these aggregations in neurons has been closely linked with several neurodegenerative diseases.

Kopito found that the mutant protein associated with Huntington's disease can leave one cell and enter another one, stirring up trouble in each new cell as it progresses down the line. The spread of the misfolded protein may explain how Huntington's progresses through the brain.

This disease, like Parkinson's and Alzheimer's, starts in one area of the brain and spreads to the rest of it. This is also similar to the spread of prions, the self-replicating proteins implicated in mad cow disease and, in humans, Creutzfeldt-Jakob disease. As the misfolded protein reaches more parts of the brain, it could be responsible for the progressive worsening of these diseases.

Now that we know that these misfolded proteins spend part of their time outside of cells, traveling from one cell to another, new drugs could target them there, Kopito said. This could help prevent or at least
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-1944
Stanford University
Source:Eurekalert  

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