title: Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition.
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.
authors.affiliation: 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
authors.forename: Rina
authors.initials: R
authors.lastname: Bandopadhyay
authors.forename: Ann E
authors.initials: AE
authors.lastname: Kingsbury
authors.forename: Miratul M
authors.initials: MM
authors.lastname: Muqit
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harvey
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Reid
authors.forename: Linda
authors.initials: L
authors.lastname: Kilford
authors.forename: Simone
authors.initials: S
authors.lastname: Engelender
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schlossmacher
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: David S
authors.initials: DS
authors.lastname: Latchman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harvey
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D061988:Proteasome Inhibitors; C118958:SNCAIP protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex