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Two-fisted assault on dopamine transport system may be foundation of Parkinson's disease

BUFFALO, N.Y. -- Parkinson's disease may be caused by an environmental-genetic double whammy on the neurons that produce dopamine, the neurotransmitter that controls body movement, a new study has shown.

Researchers at the University at Buffalo, using cultures of rat neurons, have shown that the presence of mutated parkin genes, combined with the toxic effects of the chemical rotenone, results in a cascade of highly toxic free radicals, the destruction of microtubules that transport dopamine to the brain's movement cente, and eventual death of the dopamine-producing neuron.

"This study hows how an environmental toxin and a gene linked to Parkinson's disease affect the survival of dopamine neurons by dueling on a common molecular target -- microtubules -- that are critical for the survival of dopamine-producing neurons," said Jian Feng, Ph.D., assistant professor of physiology and biophysics in UB School of Medicine and Biomedical Sciences and senior author.

"Based on these findings, we have identified several ways to stabilize microtubules against the onslaught of rotenone. These results ultimately may lead to novel therapies for Parkinson's disease."

Results of the research will be presented Dec. 5 at the American Society for Cell Biology meeting in Washington D.C.

Researchers who study Parkinson's disease know that persons with a mutation in the parkin gene are at risk for the disease, and that exposure to agricultural chemicals, including rotenone, cause Parkinson's-like symptoms in animals. In addition, long-term epidemiological studies of Parkinson's disease patients have shown a strong link between exposure to pesticides/herbicides and increased risk of developing the disease, Feng noted.

Earlier research by several groups has shown that rotenone destroys only neurons that produce dopamine, while largely sparing neurons that produce other neurotransmitters. F
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Contact: Lois Bakjer
ljbaker@buffalo.edu
716-645-5000 x1417
University at Buffalo
3-Dec-2004


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