Department of Neuroscience, Department of Biology, Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine, and Howard Hughes Medical Institute, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
ParkinsonŐs 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 a-synuclein, a protein implicated in the pathogenesis of ParkinsonŐs 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 a-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated a-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in ParkinsonŐs disease progression.