Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition.

Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, The Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK. regtrib@ucl.ac.uk
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.
Mesh Terms:
Aged, Aged, 80 and over, Brain, Carrier Proteins, Cell Line, Tumor, Cerebral Cortex, Enzyme Inhibitors, Female, Humans, Immunohistochemistry, Lewy Bodies, Male, Microscopy, Electron, Transmission, Middle Aged, Nerve Tissue Proteins, Neurons, Parkinson Disease, Peptide Hydrolases, Proteasome Endopeptidase Complex, Substantia Nigra, Ubiquitin-Protein Ligases
Neurobiol. Dis. Nov. 01, 2005; 20(2);401-11 [PUBMED:15894486]
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