Zhang Lu, Tang Yufen, Huang Peng, Luo Senlin, She Zhou, Peng Hong, Chen Yuqiong, Luo Jinwen, Duan Wangxin, Xiong Jie, Liu Lingjuan, Liu Liqun
Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
Department of Pediatric Neurology, Children's Medical Center, The Second Xiangya Hospital of Central South University, Changsha, HuChina, 410011, China.
Cell Biosci. 2024 Jun 7;14(1):75. doi: 10.1186/s13578-024-01256-y.
The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.
中枢神经系统（CNS）是人体中最脆弱的系统，其结构和功能最为复杂。它易受创伤、感染、神经退行性变和自身免疫性疾病影响，并激活免疫系统。适度的炎症反应有助于抵御入侵的微生物，而过度的炎症反应则会加重组织损伤。NLRP3炎性小体是最早在脑中被研究的炎性小体。一旦被启动和激活，它就会完成炎性小体（传感器NLRP3、接头蛋白ASC和效应蛋白半胱天冬酶-1）的组装，导致半胱天冬酶-1激活，下游炎性细胞因子释放增加，并引发细胞焦亡。累积研究证实，NLRP3在调节固有免疫和自身免疫性疾病中起重要作用，其抑制剂在各种炎性疾病的动物模型中已显示出良好疗效。在本综述中，我们将简要讨论NLRP3炎性小体的生物学特性，总结NLRP3炎性小体在中枢神经系统感染性、炎性、免疫性、退行性、遗传性和血管性疾病中的最新进展及临床影响，并讨论NLRP3作为中枢神经系统疾病治疗靶点的潜力和挑战。
