College of Animal Science and Technology, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, Zhejiang A&F University, Lin'an, 311300, Zhejiang, PR China.
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, PR China.
Cell Death Dis. 2019 Feb 12;10(2):128. doi: 10.1038/s41419-019-1413-8.
The NLRP3 inflammasome is a multimeric protein complex that initiates an inflammatory form of cell death and triggers the release of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome has been implicated in a wide range of diseases, including Alzheimer's disease, Prion diseases, type 2 diabetes, and some infectious diseases. It has been found that a variety of stimuli including danger-associated molecular patterns (DAMPs, such as silica and uric acid crystals) and pathogen-associated molecular patterns (PAMPs) can activate NLRP3 inflammasome, but the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Understanding the mechanisms of NLRP3 activation will enable the development of its specific inhibitors to treat NLRP3-related diseases. In this review, we summarize current understanding of the regulatory mechanisms of NLRP3 inflammasome activation as well as inhibitors that specifically and directly target NLRP3.
NLRP3 炎性小体是一种多聚体蛋白复合物，它启动细胞死亡的炎症形式，并引发促炎细胞因子 IL-1β 和 IL-18 的释放。NLRP3 炎性小体与多种疾病有关，包括阿尔茨海默病、朊病毒病、2 型糖尿病和一些传染病。已经发现，多种刺激物，包括危险相关分子模式（DAMPs，如二氧化硅和尿酸晶体）和病原体相关分子模式（PAMPs），可以激活 NLRP3 炎性小体，但 NLRP3 炎性小体激活的具体调节机制尚不清楚。了解 NLRP3 激活的机制将能够开发其特异性抑制剂来治疗 NLRP3 相关疾病。在这篇综述中，我们总结了 NLRP3 炎性小体激活的调节机制以及特异性和直接靶向 NLRP3 的抑制剂的最新认识。
