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Scientists develop transgenic mouse that models Parkinson's, related disorders

The first mouse model genetically programmed to simulate motor deficits and brain alterations found in Parkinson's disease and related disorders has been developed by a team of scientists at the University of California, San Diego; the University of California, San Francisco, and the Gladstone Institute of Neurological Disease. The research was led by Eliezer Masliah, M.D., of the UCSD Departments of Neurosciences and Pathology.

The investigators report in the Feb. 18 issue of Science that mice bred to express a human protein called alpha-synuclein in the brain develop protein deposits in specific brain regions associated with Parkinson's disease, and also have impaired motor function.

"Previous studies have shown increased levels of this protein in the brain cells of Parkinson's patients, but whether they were a cause or result of the disease has not been clear," said Masliah. "With these results we have demonstrated that alpha-synuclein is in fact involved in the onset of diseases such as Parkinson's. The development of symptoms in these genetically altered mice resembles disease progression in humans. This gives us a new model for studying Parkinson's disease and related disorders such as Alzheimer's disease."

The overexpression of alpha-synuclein in the brain cells of the mice is consistent with the accumulation of this protein in Parkinson's patients. Alzheimer's disease is also characterized by an abnormal accumulation of proteins in neurons, and Alzheimer's and Parkinson's disease frequently overlap.

"For many of the chemical and pathological changes one finds in brain diseases, it is hard to tell if they are a cause or consequence of the disease," said study co-author Lennart Mucke, M.D., Professor of Neurology and Neuroscience at UCSF and Director of the Gladstone Institute of Neurological Disease in San Francisco. "Our findings in experimental models demonstrate for the first time that accumulation of human alpha-synuclien in n
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Contact: Leslie Franz
lfranz@ucsd.edu
619-543-6163
University of California - San Diego
17-Feb-2000


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