Misfolded Protein Linked to Neurodegenerative Diseases

Scientists have identified a misfolded mutant protein that is associated with Huntington's, Parkinson's and Alzheimer's disease. The misfolded protein corrupts other proteins and forms large aggregations that leads to incurable neurodegenerative diseases. Stanford biology Professor Ron Kopito has shown that the mutant, misfolded protein responsible for Huntington's disease can move from cell to cell, recruiting normal proteins and forming aggregations in each cell it visits.

Knowing that this protein spends part of its time outside cells "opens up the possibility for therapeutics," said Kopito.

Kopito studied how such misfolded proteins get across a cell's membrane and into its cytoplasm, where they can interact with normal proteins. He is also investigating how these proteins move between neuronal cells.

The ability of these proteins to move from one cell to another could explain the way Huntington's disease spreads through the brain after starting in a specific region. Similar mechanisms may be involved in the progress of Parkinson's and Alzheimer's through the brain.

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.

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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, said Kopito.

The findings were discussed at the annual meeting of the American Association for the Advancement of Science in Washington.

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Source-ANI