Philadelphia -- New evidence links oxidative damage in a protein found in nerve cells to the development of degenerative diseases of the nervous system, such as Parkinson's and Alzheimer's. The first study to provide this evidence, conducted by University of Pennsylvania researchers, will be published in the November 3 issue of Science.

"The protein, called alpha-synuclein, is one of the building blocks of the brain lesions characteristic in patients with neurodegenerative diseases," says Dr. Virginia Lee, who is the John H. Ware III Professor in Alzheimer Research and co-director of the Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine at the University of Pennsylvania School of Medicine. Oxidative damage, she explains, normally occurs when the body's cells are overwhelmed by molecules that have changed because they have combined with nitrogen (nitration) or oxygen (oxidation).

Both types of oxidants damage lipids, nucleic acids, proteins, and other cellular components much like oxidation causes rust damage to metal in cars and buildings. This damage has been implicated in causing neurodegenerative disorders.

"We found that alpha-synuclein itself is a target of oxidative stress, specifically nitration, within these lesions, " says Lee. "This is the first time anybody has identified nitration on a specific protein."

Neurodegenerative diseases -- including Parkinson's, Alzheimer's, diffuse Lewy body disease, and multiple system atrophy -- are collectively called synucleinopathies. Most commonly they become symptomatic due to a deficiency of a specific neurotransmitter -- in the case of Parkinson's it is dopamine. When the neurons that produce these chemicals die or become impaired, which occurs with oxidation, the eventual results are tremors and sometimes dementia.

"Alpha-synuclein is found at the synapses of nerve cells," explains Lee. Earlier studies showed that two mutati
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Contact: Ellen O'Brien
ellen.obrien@uphs.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
1-Nov-2000