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A Drosophila model of Parkinson's disease

Abstract

Parkinson's disease is a common neurodegenerative syndrome characterized by loss of dopaminergic neurons in the substantia nigra, formation of filamentous intraneuronal inclusions (Lewy bodies) and an extrapyramidal movement disorder. Mutations in the α-synuclein gene are linked to familial Parkinson's disease1,2 and α-synuclein accumulates in Lewy bodies and Lewy neurites3,4,5. Here we express normal and mutant forms of α-synuclein in Drosophila and produce adult-onset loss of dopaminergic neurons, filamentous intraneuronal inclusions containing α-synuclein and locomotor dysfunction. Our Drosophila model thus recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease.

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Figure 1: Histological and immunocytochemical analysis of α-synuclein transgenic flies.
Figure 2: Electron microscopy of α-synuclein inclusions in flies.
Figure 3: Premature loss of climbing ability in α-synuclein transgenic flies.
Figure 4: Retinal degeneration in α-synuclein transgenic flies.

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Acknowledgements

We thank J. Hirsh, J. Hardy, M. Farrer and H. Orr for flies and DNAs; J. Hirsh, D. Dickson, M. Frosch, K. Buckley, W. Quinn and D. Morisato for discussions; and H. Shing, L. Trakimas, A. Merola, C. Ridolfi and M. Ericsson for technical assistance. M.B.F. thanks J. Gusella and the American Parkinson Disease Foundation for encouragement. Support was provided by a Howard Hughes Physician Postdoctoral Fellowship and a grant from the N.I.A. to M.B.F, and by a grant from the N.I.H. to W.B.

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Correspondence to Mel B. Feany.

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Feany, M., Bender, W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000). https://doi.org/10.1038/35006074

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