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Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway
Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876108/ https://www.ncbi.nlm.nih.gov/pubmed/24351814 http://dx.doi.org/10.3390/ijms141224242 |
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author | Li, Da Shi, Ji-Jun Mao, Cheng-Jie Liu, Sha Wang, Jian-Da Chen, Jing Wang, Fen Yang, Ya-Ping Hu, Wei-Dong Hu, Li-Fang Liu, Chun-Feng |
author_facet | Li, Da Shi, Ji-Jun Mao, Cheng-Jie Liu, Sha Wang, Jian-Da Chen, Jing Wang, Fen Yang, Ya-Ping Hu, Wei-Dong Hu, Li-Fang Liu, Chun-Feng |
author_sort | Li, Da |
collection | PubMed |
description | Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of misfolded proteins and damaged organells. Previous studies reported that dynein dysfuntion was associated with aberrant aggregation of α-synuclein, which is a major component of inclusion bodies in Parkinson’s disease (PD). However, it remains unclear what roles dynein plays in α-synuclein degradation. Our study demonstrated a decrease of dynein expression in neurotoxin-induced PD models in vitro and in vivo, accompanied by an increase of α-synuclein protein level. Dynein down-regulation induced by siRNA resulted in a prolonged half-life of α-synuclein and its over-accumulation in A53T overexpressing PC12 cells. Dynein knockdown also prompted the increase of microtubule-associated protein 1 light chain 3 (LC3-II) and sequestosome 1 (SQSTM1, p62) expression, and the accumulation of autophagic vacuoles. Moreover, dynein suppression impaired the autophagosome fusion with lysosome. In summary, our findings indicate that dynein is critical for the clearance of aberrant α-synuclein via autophagosome-lysosome pathway. |
format | Online Article Text |
id | pubmed-3876108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-38761082013-12-31 Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway Li, Da Shi, Ji-Jun Mao, Cheng-Jie Liu, Sha Wang, Jian-Da Chen, Jing Wang, Fen Yang, Ya-Ping Hu, Wei-Dong Hu, Li-Fang Liu, Chun-Feng Int J Mol Sci Article Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of misfolded proteins and damaged organells. Previous studies reported that dynein dysfuntion was associated with aberrant aggregation of α-synuclein, which is a major component of inclusion bodies in Parkinson’s disease (PD). However, it remains unclear what roles dynein plays in α-synuclein degradation. Our study demonstrated a decrease of dynein expression in neurotoxin-induced PD models in vitro and in vivo, accompanied by an increase of α-synuclein protein level. Dynein down-regulation induced by siRNA resulted in a prolonged half-life of α-synuclein and its over-accumulation in A53T overexpressing PC12 cells. Dynein knockdown also prompted the increase of microtubule-associated protein 1 light chain 3 (LC3-II) and sequestosome 1 (SQSTM1, p62) expression, and the accumulation of autophagic vacuoles. Moreover, dynein suppression impaired the autophagosome fusion with lysosome. In summary, our findings indicate that dynein is critical for the clearance of aberrant α-synuclein via autophagosome-lysosome pathway. Molecular Diversity Preservation International (MDPI) 2013-12-13 /pmc/articles/PMC3876108/ /pubmed/24351814 http://dx.doi.org/10.3390/ijms141224242 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Li, Da Shi, Ji-Jun Mao, Cheng-Jie Liu, Sha Wang, Jian-Da Chen, Jing Wang, Fen Yang, Ya-Ping Hu, Wei-Dong Hu, Li-Fang Liu, Chun-Feng Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
title | Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
title_full | Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
title_fullStr | Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
title_full_unstemmed | Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
title_short | Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway |
title_sort | alteration of dynein function affects α-synuclein degradation via the autophagosome-lysosome pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876108/ https://www.ncbi.nlm.nih.gov/pubmed/24351814 http://dx.doi.org/10.3390/ijms141224242 |
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