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Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson’s disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findin...

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Autores principales: Li, Yunna, Xia, Yun, Yin, Sijia, Wan, Fang, Hu, Junjie, Kou, Liang, Sun, Yadi, Wu, Jiawei, Zhou, Qiulu, Huang, Jinsha, Xiong, Nian, Wang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531525/
https://www.ncbi.nlm.nih.gov/pubmed/34691027
http://dx.doi.org/10.3389/fimmu.2021.719807
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author Li, Yunna
Xia, Yun
Yin, Sijia
Wan, Fang
Hu, Junjie
Kou, Liang
Sun, Yadi
Wu, Jiawei
Zhou, Qiulu
Huang, Jinsha
Xiong, Nian
Wang, Tao
author_facet Li, Yunna
Xia, Yun
Yin, Sijia
Wan, Fang
Hu, Junjie
Kou, Liang
Sun, Yadi
Wu, Jiawei
Zhou, Qiulu
Huang, Jinsha
Xiong, Nian
Wang, Tao
author_sort Li, Yunna
collection PubMed
description According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson’s disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.
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spelling pubmed-85315252021-10-23 Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease Li, Yunna Xia, Yun Yin, Sijia Wan, Fang Hu, Junjie Kou, Liang Sun, Yadi Wu, Jiawei Zhou, Qiulu Huang, Jinsha Xiong, Nian Wang, Tao Front Immunol Immunology According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson’s disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation. Frontiers Media S.A. 2021-10-08 /pmc/articles/PMC8531525/ /pubmed/34691027 http://dx.doi.org/10.3389/fimmu.2021.719807 Text en Copyright © 2021 Li, Xia, Yin, Wan, Hu, Kou, Sun, Wu, Zhou, Huang, Xiong and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Li, Yunna
Xia, Yun
Yin, Sijia
Wan, Fang
Hu, Junjie
Kou, Liang
Sun, Yadi
Wu, Jiawei
Zhou, Qiulu
Huang, Jinsha
Xiong, Nian
Wang, Tao
Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
title Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
title_full Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
title_fullStr Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
title_full_unstemmed Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
title_short Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
title_sort targeting microglial α-synuclein/tlrs/nf-kappab/nlrp3 inflammasome axis in parkinson’s disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531525/
https://www.ncbi.nlm.nih.gov/pubmed/34691027
http://dx.doi.org/10.3389/fimmu.2021.719807
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