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Findings aid understanding of neurodegenerative diseases

EVANSTON, Ill. -- Northwestern University scientists have made a key molecular discovery that has implications for a wide range of diseases characterized by the loss of nerve function, including Huntington's, Parkinson's, Alzheimer's and Lou Gehrig's diseases, cystic fibrosis and Creutzfeldt-Jakob disease, the human form of mad cow disease.

The findings, which will be published in the Oct. 1 issue of Nature Cell Biology, could lead to an understanding of how to prevent these diseases and to the development of effective drugs.

All human neurodegenerative diseases have two things in common. First, misfolded and damaged proteins clump together to form toxic species that aggregate, destroy cell function and cause disease. Second, studies have shown that special protective proteins, called molecular chaperones, can suppress these toxic effects. This question remained: How do the chaperones and aggregates interact with each other?

A research team led by Richard I. Morimoto, John Evans Professor of Biology, now can answer that question. The researchers have become the first to view, in living cells and in real time, the interactions between the beneficial molecular chaperone Hsp70 and the damaging protein aggregate, shedding light on how the chaperone works to minimize aggregate growth.

"We now understand how the chaperone influences the aggregate's toxic effect on the cell," said Morimoto. "We observed that the chaperone is binding to and then coming off the aggregate all the time. This dynamic relationship is unusual because the aggregate, the result of a genetic mutation, brings healthy and otherwise normal proteins to aggregate irreversibly with them. But this clearly is not the case with the molecular chaperone."

Instead, the molecular chaperone is allowed, for reasons not fully understood, to do its work preventing healthy proteins essential to cell function from being bound to the aggregate, a biochemical "black hole."
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
29-Sep-2002


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