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 alpha-synuclein gene are linked to familial Parkinson's disease and alpha-synuclein accumulates in Lewy bodies and Lewy neurites. Here we express normal and mutant forms of alpha-synuclein in Drosophila and produce adult-onset loss of dopaminergic neurons, filamentous intraneuronal inclusions containing alpha-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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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Cloning, Molecular
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Disease Models, Animal*
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Dopamine / metabolism
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Drosophila*
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Humans
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Inclusion Bodies / pathology
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Lewy Bodies / pathology
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Locomotion
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Mutation
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Nerve Degeneration
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / physiology
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Nerve Tissue Proteins / ultrastructure
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Neurons / metabolism
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Parkinson Disease* / etiology
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Parkinson Disease* / genetics
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Parkinson Disease* / pathology
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Retinal Degeneration / etiology
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Retinal Degeneration / pathology
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Serotonin / metabolism
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Synucleins
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Tyrosine 3-Monooxygenase / metabolism
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alpha-Synuclein
Substances
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Nerve Tissue Proteins
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SNCA protein, human
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Synucleins
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alpha-Synuclein
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Serotonin
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Tyrosine 3-Monooxygenase
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Dopamine