Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition.
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.
Bandopadhyay
Rina
R
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
Kingsbury
Ann E
AE
Muqit
Miratul M
MM
Harvey
Kirsten
K
Reid
Andrew R
AR
Kilford
Linda
L
Engelender
Simone
S
Schlossmacher
Michael G
MG
Wood
Nicholas W
NW
Latchman
David S
DS
Harvey
Robert J
RJ
Lees
Andrew J
AJ
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*
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