Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes.
Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes.
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DOI：
10.3390/ijms22020872
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发表时间：
2021-01-16
影响因子：
5.6
通讯作者：
de Alba E
中科院分区：
文献类型：
--
作者：
Sharma M;de Alba E
炎性小体是一种三组分（传感器、适配器和效应器）丝状信号传导平台，其通过刺激促炎细胞因子的蛋白水解成熟和焦变性细胞死亡来屏蔽多种病原性感染。信号传导过程起始于特异性传感器检测内源性和/或外部危险信号，随后是从传感器到下游适配器，然后到效应器caspase-1的成核和聚合。炎性小体的异常激活促进自身炎性疾病、癌症、神经变性和心脏代谢紊乱。因此，需要公平水平的调节来维持炎性小体激活和抑制之间的平衡。炎性小体组装的结构和机制理解的最新进展加强了针对炎性小体调节的疾病的新疗法的出现。本文综述了近年来对炎性小体组分的结构、活化、相互作用、调控机制以及形成致密丝状炎性小体复合体的研究进展，并对炎性小体复合体介导免疫反应的机制进行了探讨。
The inflammasome is a three-component (sensor, adaptor, and effector) filamentous signaling platform that shields from multiple pathogenic infections by stimulating the proteolytical maturation of proinflammatory cytokines and pyroptotic cell death. The signaling process initiates with the detection of endogenous and/or external danger signals by specific sensors, followed by the nucleation and polymerization from sensor to downstream adaptor and then to the effector, caspase-1. Aberrant activation of inflammasomes promotes autoinflammatory diseases, cancer, neurodegeneration, and cardiometabolic disorders. Therefore, an equitable level of regulation is required to maintain the equilibrium between inflammasome activation and inhibition. Recent advancement in the structural and mechanistic understanding of inflammasome assembly potentiates the emergence of novel therapeutics against inflammasome-regulated diseases. In this review, we have comprehensively discussed the recent and updated insights into the structure of inflammasome components, their activation, interaction, mechanism of regulation, and finally, the formation of densely packed filamentous inflammasome complex that exists as micron-sized punctum in the cells and mediates the immune responses.
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