Science 2002 Feb 1;295(5556):865-8

Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease.

Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM. Department of Neuroscience, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

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 alpha-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 alpha-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated alpha-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.