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Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease

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Science  01 Feb 2002:
Vol. 295, Issue 5556, pp. 865-868
DOI: 10.1126/science.1067389

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Abstract

Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with α-synuclein in Drosophilaand that interference with endogenous chaperone activity accelerated α-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression.

  • * Present address: Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong.

  • To whom correspondence should be addressed. E-mail: nbonini{at}sas.upenn.edu

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