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 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.
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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Brain Chemistry
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Disease Models, Animal*
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Dopamine / metabolism
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Drosophila Proteins*
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Drosophila melanogaster* / genetics
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Female
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HSC70 Heat-Shock Proteins
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HSP40 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins / analysis
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism*
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Heat-Shock Proteins / analysis
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism*
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Humans
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Inclusion Bodies / chemistry
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Inclusion Bodies / ultrastructure
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Lewy Bodies / chemistry
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Lewy Bodies / ultrastructure
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Male
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Nerve Degeneration
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / pathology
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Neurons / physiology*
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Parkinsonian Disorders* / genetics
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Parkinsonian Disorders* / metabolism
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Parkinsonian Disorders* / pathology
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Synucleins
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Transgenes
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alpha-Synuclein
Substances
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Drosophila Proteins
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HSC70 Heat-Shock Proteins
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HSP40 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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Heat-Shock Proteins
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Hsc70-4 protein, Drosophila
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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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Dopamine