Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson's Disease.
Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson's Disease.
复制标题
帕金森病小胶质细胞α-突触核蛋白/TLRs/核因子-kappaB/NLRP3炎症体轴靶向研究
DOI：
10.3389/fimmu.2021.719807
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Li Y;Xia Y;Yin S;Wan F;Hu J;Kou L;Sun Y;Wu J;Zhou Q;Huang J;Xiong N;Wang T
新的研究表明，小胶质细胞的过度激活和随后的促炎细胞因子的释放在帕金森病(PD)的发生和发展中起着重要的作用。然而，控制慢性神经炎的确切机制仍然不清楚。结果显示PD患者黑质激活的小胶质细胞中NLRP3炎性小体水平升高。激活的NLRP3炎性小体加重了病理，加速了神经退行性疾病的进展。α-突触核蛋白的异常蛋白聚集(α-SYN)是帕金森病的病理相关蛋白，通过与Toll样受体(TLRs)相互作用，激活小胶质细胞的NLRP3炎性小体。这最终通过核因子kappaB(NF-κB)的易位释放促炎细胞因子，导致线粒体损伤，从而损伤多巴胺能神经元。目前，治疗帕金森病的药物主要是为了缓解其临床症状，目前还没有成熟的战略来阻止或逆转这种疾病。本文就α-SYN/TLRS/NF-κB/NLRP3炎性小体轴和小胶质细胞激活在帕金森病发病中的作用进行综述。此外，本文还综述了小胶质细胞α-SYN/TLRS/NF-κB/NLRP3炎性小体轴作为抑制小胶质细胞活化治疗帕金森病的潜在靶点的研究进展。
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.