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Scientists find solution to a mystery surrounding Alzheimers, Huntington's and other neurological diseases

Stanford researchers have found an answer to a long-standing mystery surrounding Huntingtons, Alzheimers, Parkinsons and other neurodegenerative diseases.

Their discovery, published in the May 25 issue of the journal Science, focuses on one of the telltale signs of neurodegenerative illness: the mysterious buildup of defective proteins in and around nerve cells.

Healthy cells have the ability to break down and eliminate unwanted proteins. But in neurodegenerative diseases, abnormal proteins clump together to form clusters called aggregates that interfere with the cells normal functions.

Its been known for years that most neurodegenerative diseases are associated with protein aggregates, says Ron R. Kopito, professor of biological sciences and co-author of the study, but no one had a clue as to the exact relationship. Do aggregates cause the disease, or are they the result of the disease?

To find out, Kopito and graduate student Neil F. Bence designed a laboratory experiment to assess the impact of protein aggregates on the inner workings of a cell.

Master controller

Their specific target was the proteasome a barrel-shaped enzyme that Kopito calls the master controller of the cell.

The proteasome is like a salami slicer that cuts protein molecules into little bits, he says. It gets rid of abnormal proteins, and it breaks down and recycles regulatory proteins no longer needed by the cell.

Human cells contain thousands of proteins, each with a unique three-dimensional shape determined by specific genes. But random genetic errors and mutations may cause proteins to fold into the wrong 3-D configuration - often with devastating results.

One example is huntingtin a protein found in healthy nerve cells. A slight genetic mutation may cause huntingtin proteins to fold incorrectly and accumulate inside the nerve. Defective huntingtin aggregates are common in patients with Huntingtons disease.

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Contact: Mark Shwartz
mshwartz@stanford.edu
650-723-9296
Stanford University
23-May-2001


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