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BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease
BACKGROUND: Neuroinflammation mediated by microglia plays a key role in the pathogenesis of Parkinson’s disease (PD), and our previous studies showed this was significantly inhibited by enhanced autophagy. In the autophagy pathway, Bcl2-associated athanogene (BAG)3 is a prominent co-chaperone, and w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761134/ https://www.ncbi.nlm.nih.gov/pubmed/36544667 http://dx.doi.org/10.21037/atm-22-5159 |
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author | Ying, Zhong-Ming Lv, Qian-Kun Yao, Xiao-Yu Dong, An-Qi Yang, Ya-Ping Cao, Yu-Lan Wang, Fen Gong, Ai-Ping Liu, Chun-Feng |
author_facet | Ying, Zhong-Ming Lv, Qian-Kun Yao, Xiao-Yu Dong, An-Qi Yang, Ya-Ping Cao, Yu-Lan Wang, Fen Gong, Ai-Ping Liu, Chun-Feng |
author_sort | Ying, Zhong-Ming |
collection | PubMed |
description | BACKGROUND: Neuroinflammation mediated by microglia plays a key role in the pathogenesis of Parkinson’s disease (PD), and our previous studies showed this was significantly inhibited by enhanced autophagy. In the autophagy pathway, Bcl2-associated athanogene (BAG)3 is a prominent co-chaperone, and we have shown BAG3 can regulate autophagy to clear the PD pathogenic protein α-synuclein. However, the connection between BAG3 and microglia mediated neuroinflammation is not clear. METHODS: In this study, we explored whether BAG3 regulated related neuroinflammation and its original mechanism in PD. An inflammatory model of PD was established by injecting adeno-associated virus (AAV)-BAG3 into the bilateral striatum of C57BL/6 male mice to induce overexpression of BAG3, followed by injection of lipopolysaccharide (LPS). The striatum was extracted at 3 days after injection of LPS for Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemical staining was performed at 21 days after injection. At the same time, LPS was used to induce activation of BV2 cells to verify the effect of BAG3 in vitro. RESULTS: Overexpression of BAG3 reduced LPS-induced pyroptosis by reducing activation of caspase-1, the NOD-like receptor family, and the pyrin domain-containing 3 (NLRP3) inflammasome, and by release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The LPS-induced inflammatory environment inhibits autophagy, and overexpression of BAG3 can restore autophagy, which may be the mechanism by which BAG3 reduces neuronal inflammation in PD. CONCLUSIONS: Our results demonstrate BAG3 promotes autophagy and suppresses NLRP3 inflammasome formation in PD. |
format | Online Article Text |
id | pubmed-9761134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-97611342022-12-20 BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease Ying, Zhong-Ming Lv, Qian-Kun Yao, Xiao-Yu Dong, An-Qi Yang, Ya-Ping Cao, Yu-Lan Wang, Fen Gong, Ai-Ping Liu, Chun-Feng Ann Transl Med Original Article BACKGROUND: Neuroinflammation mediated by microglia plays a key role in the pathogenesis of Parkinson’s disease (PD), and our previous studies showed this was significantly inhibited by enhanced autophagy. In the autophagy pathway, Bcl2-associated athanogene (BAG)3 is a prominent co-chaperone, and we have shown BAG3 can regulate autophagy to clear the PD pathogenic protein α-synuclein. However, the connection between BAG3 and microglia mediated neuroinflammation is not clear. METHODS: In this study, we explored whether BAG3 regulated related neuroinflammation and its original mechanism in PD. An inflammatory model of PD was established by injecting adeno-associated virus (AAV)-BAG3 into the bilateral striatum of C57BL/6 male mice to induce overexpression of BAG3, followed by injection of lipopolysaccharide (LPS). The striatum was extracted at 3 days after injection of LPS for Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemical staining was performed at 21 days after injection. At the same time, LPS was used to induce activation of BV2 cells to verify the effect of BAG3 in vitro. RESULTS: Overexpression of BAG3 reduced LPS-induced pyroptosis by reducing activation of caspase-1, the NOD-like receptor family, and the pyrin domain-containing 3 (NLRP3) inflammasome, and by release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The LPS-induced inflammatory environment inhibits autophagy, and overexpression of BAG3 can restore autophagy, which may be the mechanism by which BAG3 reduces neuronal inflammation in PD. CONCLUSIONS: Our results demonstrate BAG3 promotes autophagy and suppresses NLRP3 inflammasome formation in PD. AME Publishing Company 2022-11 /pmc/articles/PMC9761134/ /pubmed/36544667 http://dx.doi.org/10.21037/atm-22-5159 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Ying, Zhong-Ming Lv, Qian-Kun Yao, Xiao-Yu Dong, An-Qi Yang, Ya-Ping Cao, Yu-Lan Wang, Fen Gong, Ai-Ping Liu, Chun-Feng BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease |
title | BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease |
title_full | BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease |
title_fullStr | BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease |
title_full_unstemmed | BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease |
title_short | BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson’s disease |
title_sort | bag3 promotes autophagy and suppresses nlrp3 inflammasome activation in parkinson’s disease |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761134/ https://www.ncbi.nlm.nih.gov/pubmed/36544667 http://dx.doi.org/10.21037/atm-22-5159 |
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