Abstract
Lewy bodies (LBs) are the characteristic inclusions of Parkinson's disease brain but the mechanism responsible for their formation is obscure. Lewy bodies (LBs) are composed of a number of proteins of which alpha-synuclein (alpha-SYN) is a major constituent. In this study, we have investigated the distribution patterns of synphilin-1 and parkin proteins in control and sporadic PD brain tissue by immunohistochemistry (IH), immunoblotting, and immunoelectron microscopy (IEM). We demonstrate the presence of synphilin-1 and parkin in the central core of a majority of LBs using IH and IEM. Using IH, we show an overlapping distribution profile of the two proteins in central neurons. Additionally, we show sensitivity of both endogenous synphilin-1 and parkin to proteolytic dysfunction and their co-localization in aggresomes formed in response to the proteasome inhibitor MG-132. We confirm that synphilin-1 and parkin are components of majority of LBs in Parkinson's disease and that both proteins are susceptible to proteasomal degradation.
Publication types
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Research Support, N.I.H., Extramural
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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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Aged
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Aged, 80 and over
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Brain / metabolism*
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Brain / pathology
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Brain / physiopathology
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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Cerebral Cortex / metabolism
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Cerebral Cortex / pathology
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Cerebral Cortex / physiopathology
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Enzyme Inhibitors / pharmacology
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Female
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Humans
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Immunohistochemistry
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Lewy Bodies / metabolism*
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Lewy Bodies / pathology
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Lewy Bodies / ultrastructure
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Male
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Microscopy, Electron, Transmission
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Middle Aged
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism
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Neurons / pathology
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Neurons / ultrastructure
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Parkinson Disease / metabolism*
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Parkinson Disease / pathology
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Parkinson Disease / physiopathology
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Peptide Hydrolases / metabolism
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Proteasome Endopeptidase Complex / metabolism*
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Proteasome Inhibitors
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Substantia Nigra / metabolism
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Substantia Nigra / pathology
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Substantia Nigra / physiopathology
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Ubiquitin-Protein Ligases / metabolism*
Substances
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Carrier Proteins
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Enzyme Inhibitors
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Nerve Tissue Proteins
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Proteasome Inhibitors
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SNCAIP protein, human
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Ubiquitin-Protein Ligases
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parkin protein
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Peptide Hydrolases
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Proteasome Endopeptidase Complex