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 (α-SYN) is a major constituent. In this study, we have investigated the...
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doaj-6f0ed25c8e0f4630918b13e8184398302021-03-20T04:51:15ZengElsevierNeurobiology of Disease1095-953X2005-11-01202401411Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibitionRina Bandopadhyay0Ann E. Kingsbury1Miratul M. Muqit2Kirsten Harvey3Andrew R. Reid4Linda Kilford5Simone Engelender6Michael G. Schlossmacher7Nicholas W. Wood8David S. Latchman9Robert J. Harvey10Andrew J. Lees11Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, The Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK; Corresponding author. Fax: +44 207 679 9429.Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, The Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK; Queen Square Brain Bank, Institute of Neurology, 1 Wakefield Street, London WC1N 3BG, UKMedical Molecular Biology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKDepartment of Pharmacology, The School of Pharmacy, 29–39 Brunswick Square, London WC1N 1AX, UKReta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, The Windeyer Building, 46 Cleveland Street, London W1T 4JF, UKQueen Square Brain Bank, Institute of Neurology, 1 Wakefield Street, London WC1N 3BG, UKDepartment of Pharmacology, Technion Israel-Institute of Technology, Haifa, IsraelDepartment of Neurology, Centre for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue, Louis Pasteur, Boston, MA 02115, USADepartment of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UKMedical Molecular Biology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; Birkbeck College, University of London, Mallet Street, London WC1E 7HX, UKDepartment of Pharmacology, The School of Pharmacy, 29–39 Brunswick Square, London WC1N 1AX, UKReta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, The Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK; Queen Square Brain Bank, Institute of Neurology, 1 Wakefield Street, London WC1N 3BG, UKLewy 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.http://www.sciencedirect.com/science/article/pii/S0969996105000926Synphilin-1ParkinLewy bodiesDistributionImmunohistochemistryImmunoelectron microscopy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rina Bandopadhyay Ann E. Kingsbury Miratul M. Muqit Kirsten Harvey Andrew R. Reid Linda Kilford Simone Engelender Michael G. Schlossmacher Nicholas W. Wood David S. Latchman Robert J. Harvey Andrew J. Lees |
spellingShingle |
Rina Bandopadhyay Ann E. Kingsbury Miratul M. Muqit Kirsten Harvey Andrew R. Reid Linda Kilford Simone Engelender Michael G. Schlossmacher Nicholas W. Wood David S. Latchman Robert J. Harvey Andrew J. Lees Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition Neurobiology of Disease Synphilin-1 Parkin Lewy bodies Distribution Immunohistochemistry Immunoelectron microscopy |
author_facet |
Rina Bandopadhyay Ann E. Kingsbury Miratul M. Muqit Kirsten Harvey Andrew R. Reid Linda Kilford Simone Engelender Michael G. Schlossmacher Nicholas W. Wood David S. Latchman Robert J. Harvey Andrew J. Lees |
author_sort |
Rina Bandopadhyay |
title |
Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition |
title_short |
Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition |
title_full |
Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition |
title_fullStr |
Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition |
title_full_unstemmed |
Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition |
title_sort |
synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2005-11-01 |
description |
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. |
topic |
Synphilin-1 Parkin Lewy bodies Distribution Immunohistochemistry Immunoelectron microscopy |
url |
http://www.sciencedirect.com/science/article/pii/S0969996105000926 |
work_keys_str_mv |
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