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

R Bandopadhyay; A E Kingsbury; M M Muqit; K Harvey; A R Reid; L Kilford; S Engelender; M G Schlossmacher; N W Wood; D S Latchman; Robert J Harvey; A J Lees

doi:10.1016/j.nbd.2005.03.021

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

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

R Bandopadhyay, A E Kingsbury, M M Muqit, K Harvey, A R Reid, L Kilford, S Engelender, M G Schlossmacher, N W Wood, D S Latchman, …

Neurobiology of Disease, Vol.20(2), pp.401-411

2005

DOI: https://doi.org/10.1016/j.nbd.2005.03.021

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Abstract

synphilin-1

parkin

lewy bodies

distribution

immunohistochemistry

immunoelectron microscopy

aggresomes

proteasome inhibitor

MG-132

yeast two-hybrid analysis

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 (α-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. © 2005 Elsevier Inc. All rights reserved.

Details

Title: Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition
Authors: R Bandopadhyay (Author) - Reta Lila Weston Institute of Neurological Studies, United Kingdom
A E Kingsbury (Author) - Reta Lila Weston Institute of Neurological Studies, United Kingdom
M M Muqit (Author) - Institute of Child Health, United Kingdom
K Harvey (Author) - University College London, United Kingdom
A R Reid (Author) - Reta Lila Weston Institute of Neurological Studies, United Kingdom
L Kilford (Author) - Institute of Neurology, United Kingdom
S Engelender (Author) - Technion Israel-Institute of Technology, Israel
M G Schlossmacher (Author) - Centre for Neurologic Diseases, United States
N W Wood (Author) - Institute of Neurology, United Kingdom
D S Latchman (Author) - Institute of Child Health, United Kingdom
Robert J Harvey (Author) - University College London, United Kingdom
A J Lees (Author) - Reta Lila Weston Institute of Neurological Studies, United Kingdom
Publication details: Neurobiology of Disease, Vol.20(2), pp.401-411
Publisher: Academic Press
Date published: 2005
DOI: 10.1016/j.nbd.2005.03.021
ISSN: 0969-9961
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450914602621
Output Type: Journal article

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Web Of Science research areas: Neurosciences

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