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DJ-1 can inhibit microtubule associated protein 1 B formed aggregates

BACKGROUND: Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation...

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Autores principales: Wang, Zhiquan, Zhang, Yu, Zhang, Shi, Guo, Qianqian, Tan, Yuyan, Wang, Xinyi, Xiong, Ran, Ding, Jianqing, Chen, Shengdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120713/
https://www.ncbi.nlm.nih.gov/pubmed/21645326
http://dx.doi.org/10.1186/1750-1326-6-38
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author Wang, Zhiquan
Zhang, Yu
Zhang, Shi
Guo, Qianqian
Tan, Yuyan
Wang, Xinyi
Xiong, Ran
Ding, Jianqing
Chen, Shengdi
author_facet Wang, Zhiquan
Zhang, Yu
Zhang, Shi
Guo, Qianqian
Tan, Yuyan
Wang, Xinyi
Xiong, Ran
Ding, Jianqing
Chen, Shengdi
author_sort Wang, Zhiquan
collection PubMed
description BACKGROUND: Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD. RESULTS: We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis. CONCLUSION: Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).
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spelling pubmed-31207132011-06-23 DJ-1 can inhibit microtubule associated protein 1 B formed aggregates Wang, Zhiquan Zhang, Yu Zhang, Shi Guo, Qianqian Tan, Yuyan Wang, Xinyi Xiong, Ran Ding, Jianqing Chen, Shengdi Mol Neurodegener Research Article BACKGROUND: Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD. RESULTS: We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis. CONCLUSION: Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD). BioMed Central 2011-06-06 /pmc/articles/PMC3120713/ /pubmed/21645326 http://dx.doi.org/10.1186/1750-1326-6-38 Text en Copyright ©2011 Wang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Zhiquan
Zhang, Yu
Zhang, Shi
Guo, Qianqian
Tan, Yuyan
Wang, Xinyi
Xiong, Ran
Ding, Jianqing
Chen, Shengdi
DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
title DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
title_full DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
title_fullStr DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
title_full_unstemmed DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
title_short DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
title_sort dj-1 can inhibit microtubule associated protein 1 b formed aggregates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120713/
https://www.ncbi.nlm.nih.gov/pubmed/21645326
http://dx.doi.org/10.1186/1750-1326-6-38
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