Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions
We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of α-synuclein (α-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D (CatD), and Heat Shock Protein73 (HSP73) immunoreac...
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doaj-bf3d20edf888427bb99553cb6bcc75d62021-03-20T04:57:42ZengElsevierNeurobiology of Disease1095-953X2009-09-01353385398Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusionsYaping Chu0Hemraj Dodiya1Patrick Aebischer2C. Warren Olanow3Jeffrey H. Kordower4Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USADepartment of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USABrain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, SwitzerlandDepartment of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USADepartment of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA; Corresponding author. Fax: +1 312 563 3571.We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of α-synuclein (α-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D (CatD), and Heat Shock Protein73 (HSP73) immunoreactivity were significantly decreased within PD nigral neurons when compared to age-matched controls. This decrease was significantly greater in nigral neurons that contained α-syn inclusions. Immunoreactivity for 20S proteasome was similarly reduced in PD nigral neurons, but only in cells that contained inclusions. In aged control brains, there is staining for α-syn protein, but it is non-aggregated and there is no difference in LAMP1, CatD, HSP73 or 20S proteasome immunoreactivity between α-syn positive or negative neuromelanin-laden nigral neurons. Targeting over-expression of mutant human α-syn in the rat substantia nigra using viral vectors revealed that lysosomal and proteasomal markers were significantly decreased in the neurons that displayed α-syn-ir inclusions. These findings suggest that α-syn aggregation is a key feature associated with decline of proteasome and lysosome and support the hypothesis that cell degeneration in PD involves proteosomal and lysosomal dysfunction, impaired protein clearance, and protein accumulation and aggregation leading to cell death.http://www.sciencedirect.com/science/article/pii/S0969996109001351Parkinson's diseaseLysosomeProteasomeAlpha-synuclein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yaping Chu Hemraj Dodiya Patrick Aebischer C. Warren Olanow Jeffrey H. Kordower |
spellingShingle |
Yaping Chu Hemraj Dodiya Patrick Aebischer C. Warren Olanow Jeffrey H. Kordower Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions Neurobiology of Disease Parkinson's disease Lysosome Proteasome Alpha-synuclein |
author_facet |
Yaping Chu Hemraj Dodiya Patrick Aebischer C. Warren Olanow Jeffrey H. Kordower |
author_sort |
Yaping Chu |
title |
Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions |
title_short |
Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions |
title_full |
Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions |
title_fullStr |
Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions |
title_full_unstemmed |
Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions |
title_sort |
alterations in lysosomal and proteasomal markers in parkinson's disease: relationship to alpha-synuclein inclusions |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2009-09-01 |
description |
We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of α-synuclein (α-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D (CatD), and Heat Shock Protein73 (HSP73) immunoreactivity were significantly decreased within PD nigral neurons when compared to age-matched controls. This decrease was significantly greater in nigral neurons that contained α-syn inclusions. Immunoreactivity for 20S proteasome was similarly reduced in PD nigral neurons, but only in cells that contained inclusions. In aged control brains, there is staining for α-syn protein, but it is non-aggregated and there is no difference in LAMP1, CatD, HSP73 or 20S proteasome immunoreactivity between α-syn positive or negative neuromelanin-laden nigral neurons. Targeting over-expression of mutant human α-syn in the rat substantia nigra using viral vectors revealed that lysosomal and proteasomal markers were significantly decreased in the neurons that displayed α-syn-ir inclusions. These findings suggest that α-syn aggregation is a key feature associated with decline of proteasome and lysosome and support the hypothesis that cell degeneration in PD involves proteosomal and lysosomal dysfunction, impaired protein clearance, and protein accumulation and aggregation leading to cell death. |
topic |
Parkinson's disease Lysosome Proteasome Alpha-synuclein |
url |
http://www.sciencedirect.com/science/article/pii/S0969996109001351 |
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