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Drug averts Parkinson's disease in fruit flies, suggesting new approach for humans

PHILADELPHIA -- Scientists at the University of Pennsylvania have averted the onset of neurodegenerative disease in fruit flies by administering medication to flies genetically predisposed to a disorder akin to Parkinson's disease.

The result suggests a new approach to the treatment of human disorders including Parkinson's and Alzheimer's diseases. Penn biologist Nancy M. Bonini and graduate student Pavan K. Auluck report the finding in the November issue of Nature Medicine.

Parkinson's disease is the second most common human neurodegenerative disorder, characterized by tremors, postural rigidity and progressive deterioration of dopaminergic neurons in specific areas of the brain. Despite the evolutionary gulf separating humans and fruit flies, neurotoxicity unfolds in a similar manner in both species. Like humans, Drosophila melanogaster experiences neuronal loss upon expression of alpha-synuclein, a protein implicated in the onset of Parkinson's disease in both species.

"Medications now prescribed to people with Parkinson's disease, such as levodopa, bromocriptine and deprenyl, relieve symptoms by rescuing neurons compromised by the disease," said Bonini, Penn professor of biology and investigator with the Howard Hughes Medical Institute. "Our studies suggest that a new class of drugs might prevent neurodegenerative disorders by fortifying these neurons even before the onset of disease."

Bonini and Auluck fed flies a naturally occurring antibiotic called geldanamycin. When fed geldanamycin-supplemented food as adults, flies with a genetic susceptibility to neurodegenerative disease -- flies that would normally experience a 50 percent loss of dopaminergic neurons by 20 days of age -- maintained normal numbers of these neurons.

Geldanamycin tweaks the activity of Hsp90, one of a class of proteins known as molecular chaperones. Bonini, Auluck and colleagues showed last year that molecular chaperones can block the prog
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Contact: Steve Bradt
bradt@pobox.upenn.edu
215-573-6604
University of Pennsylvania
11-Nov-2002


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