Abstract
Alpha-synuclein (alpha-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type alpha-syn, PD-linked mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant alpha-syn forms more beta-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of alpha-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution*
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Amyloid
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Benzothiazoles
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Biopolymers / metabolism
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Circular Dichroism
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Dimerization
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Humans
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Hydrogen-Ion Concentration
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Lewy Bodies
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Microscopy, Electron
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Mutation
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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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Nerve Tissue Proteins / ultrastructure
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Parkinson Disease / etiology
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Parkinson Disease / genetics*
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombinant Proteins / ultrastructure
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Synucleins
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Thiazoles
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alpha-Synuclein
Substances
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Amyloid
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Benzothiazoles
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Biopolymers
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Nerve Tissue Proteins
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Recombinant Proteins
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SNCA protein, human
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Synucleins
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Thiazoles
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alpha-Synuclein
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thioflavin T