PDF(Pubmed)
Abstract：
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.
摘要：
中枢神经系统(CNS)是人体最脆弱的系统,具有最复杂的结构和功能。它容易受到创伤，感染,神经变性和自身免疫性疾病，激活免疫系统.适当的炎症反应有助于防御入侵的微生物，而过度的炎症反应会加重组织损伤。NLRP3炎性体是第一个在大脑中研究的。一旦启动和激活，它完成了炎症体(传感器NLRP3，适配器ASC，和效应子caspase-1），导致caspase-1激活和下游炎性细胞因子释放增加，以及焦亡。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,及其抑制剂在各种炎症性疾病的动物模型中显示出良好的疗效。在这次审查中,我们将简要讨论NLRP3炎性体的生物学特性，总结NLRP3炎性体在感染性疾病中的最新进展和临床影响，炎症，免疫，退化,遗传,和中枢神经系统的血管疾病，并讨论了NLRP3作为CNS疾病治疗靶点的潜力和挑战。
