吡喃结构域
炎症体
细胞生物学
先天免疫系统
信号转导衔接蛋白
目标2
调节器
半胱氨酸蛋白酶1
模式识别受体
受体
化学
NALP3
半胱氨酸蛋白酶
信号转导
生物
细胞凋亡
程序性细胞死亡
生物化学
基因
作者
Ni Zhao,Cuicui Li,Bin Di,Lili Xu
标识
DOI:10.1016/j.jaut.2020.102515
摘要
The nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome is a high-molecular-weight complex mediated by the activation of pattern-recognition receptors (PRRs) seed in innate immunity. Once NLRP3 is activated, the following recruitment of the adapter apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC) and procaspase-1 would be initiated. Cleavage of procaspase-1 into active caspase-1 then leads to the maturation of the precursor forms of interleukin (IL)-1β and IL-18 into biologically active IL-1β and IL-18. The activation of NLRP3 inflammasome is thought to be tightly associated with a regulator never in mitosis A (NIMA)-related kinase 7 (NEK7), apart from other signaling events such as K+ efflux and reactive oxygen species (ROS). Plus, the NLRP3 inflammasome has been linked to various metabolic disorders, chronic inflammation and other diseases. In this review, we firstly describe the cellular/molecular mechanisms of the NEK7-licensed NLRP3 inflammasome activation. Then we detail the potential inhibitors that can selectively and effectively modulate either the NEK7-NLRP3 complex itself or the related molecular/cellular events. Finally, we describe some inhibitors as promising therapeutic strategies for diverse diseases driven by NLRP3 inflammasome.
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