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Northwestern scientists shed new light on neurodegenerative diseases

EVANSTON, Ill. -In a breakthrough study to be published in the May 23 issue of the Proceedings of the National Academy of Sciences, scientists at Northwestern University report new insights into the biological and molecular underpinnings of an entire class of neurodegenerative diseases, ranging from Huntington's and Alzheimer's diseases to cystic fibrosis and Creutzfeldt-Jakob disease, the human form of mad cow disease.

The findings provide a new model for understanding the common pathology of these diseases, knowledge that could lead to the development of effective drugs.

The diseases, characterized by the loss of nerve function, are caused by a variety of mutant genes. However, they all have one element in common: misfolded proteins that lead to protein aggregation, the accumulation of insoluble proteins that can result in toxicity and disease.

In their study, Richard I. Morimoto, John Evans Professor of Biology, and his research team zeroed in on this commonality, focusing on the dangerous protein behavior itself instead of the genes responsible. They discovered that polyglutamine aggregates (one type of protein aggregate) are indeed toxic and that these unhealthy proteins bring healthy and otherwise normal proteins to aggregate with them. The researchers also found that the growth of these aggregates can be suppressed by molecular chaperones called heat shock proteins.

"This work highlights how basic science can answer important questions in terms of human neurodegenerative diseases," said Harry Orr, professor and director of the Institute of Human Genetics at the University of Minnesota Medical School. "Humans share much of the same biology with the subject of the study, the worm called C. elegans. The question that's being asked, whether a neuron lives or dies, is a fundamental one across species."

Proteins, made up of different combinations of amino acids, are basic components of all living cells. To do their job properly, e
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
21-May-2000


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