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NLRP3 炎性体激活剂和抑制剂的分子机制研究进展。

Advances in the molecular mechanisms of NLRP3 inflammasome activators and inactivators.

机构信息

Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Department of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 510632, Guangdong, China.

出版信息

Biochem Pharmacol. 2020 May;175:113863. doi: 10.1016/j.bcp.2020.113863. Epub 2020 Feb 17.

Abstract

NLRP3 inflammasome is an intracellular protein complex that initiates cellular injury via assembly of NLRP3, ASC and caspase-1 in response to microbial infection and sterile stressors. The importance of NLRP3 inflammasome in immunity and human diseases has been well documented. Up to now, targeted inhibition of the assembly of NLRP3 inflammasome complex and of its activation was thought to be therapeutic strategy for associated diseases. Recent studies show that a host of molecules such as NIMA-related kinase 7 (Nek7) and DEAD-box helicase 3 X-linked (DDX3X) and a large number of biological mediators including cytokines, microRNAs, nitric oxide, carbon monoxide, nuclear factor erythroid-2 related factor 2 (Nrf2) and cellular autophagy participate in the activation and inactivation of NLRP3 inflammasome. This review summarizes current understanding of the molecular basis of NLRP3 inflammasome activation and inactivation. This knowledge may lead to development of new therapies directed at NLRP3 inflammasome related diseases.

摘要

NLRP3 炎性小体是一种细胞内蛋白复合物,当微生物感染和非微生物应激源激活时,NLRP3、ASC 和半胱天冬酶-1 会组装成 NLRP3 炎性小体,从而引发细胞损伤。NLRP3 炎性小体在免疫和人类疾病中的重要性已得到充分证实。到目前为止,靶向抑制 NLRP3 炎性小体复合物的组装及其激活被认为是相关疾病的治疗策略。最近的研究表明,许多分子,如 NIMA 相关激酶 7(Nek7)和 DEAD 框解旋酶 3 X 连锁(DDX3X),以及大量生物介质,包括细胞因子、microRNAs、一氧化氮、一氧化碳、红细胞生成核因子 2 相关因子 2(Nrf2)和细胞自噬,参与 NLRP3 炎性小体的激活和失活。本文综述了 NLRP3 炎性小体激活和失活的分子基础的最新认识。这些知识可能会促使针对 NLRP3 炎性小体相关疾病的新疗法的发展。

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