Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease

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 α-synuclein, a protein implicated in the pathogenesis of Parkinso...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2002-02, Vol.295 (5556), p.865-868
Main Authors: Auluck, Pavan K., H. Y. Edwin Chan, Trojanowski, John Q., Virginia M.-Y. Lee, Bonini, Nancy M.
Format: Article
Language:English
Subjects:
a-Synuclein
alpha-Synuclein
Animals
Animals, Genetically Modified
Antibodies
Behavioral neuroscience
Biological and medical sciences
Brain
Brain Chemistry
Degeneration
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Dopamine - metabolism
Dopaminergic neurons
Drosophila
Drosophila melanogaster - genetics
Drosophila Proteins
Female
Genetic aspects
Heat-Shock Proteins - analysis
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
HSC70 Heat-Shock Proteins
HSP40 Heat-Shock Proteins
HSP70 Heat-Shock Proteins - analysis
HSP70 Heat-Shock Proteins - genetics
HSP70 Heat-Shock Proteins - metabolism
Humans
Inclusion Bodies - chemistry
Inclusion Bodies - ultrastructure
Insects
Lewy Bodies - chemistry
Lewy Bodies - ultrastructure
Male
Medical sciences
Molecules
Nerve Degeneration
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nervous system
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
Neurogenetics
Neurology
Neurons
Neurons - physiology
Parkinson disease
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson's disease
Parkinsonian Disorders - genetics
Parkinsonian Disorders - metabolism
Parkinsonian Disorders - pathology
Pathology
Saccades
Synucleins
Transgenes
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Description
Summary: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 α-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 α-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated α-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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1067389