NLRP炎性体是一组胞质多蛋白寡聚体模式识别受体(PRR),参与识别由感染细胞产生的病原体相关分子模式(PAMP)和危险相关分子模式(DAMP)。它们通过触发保护性炎症反应来调节先天免疫。然而,尽管有保护作用,NLRP传感蛋白中的异常NLPR炎性体激活和功能获得突变参与非通信自身免疫的发生和增强,自身炎症,和神经退行性疾病。在过去的几年里,在理解NLRP炎性体生理功能及其激活的分子机制方面取得了重大进展,以及针对炎症性疾病中NLRP炎性体活性的疗法。这里,我们提供了NLRP炎性体的最新研究进展,包括NLRP1、CARD8、NLRP3、NLRP6、NLRP7、NLRP2、NLRP9、NLRP10和NLRP12关于它们的结构和组装特征,信号转导和分子激活机制。重要的是,我们强调了与许多人类自身炎症相关的NLRP炎性体失调的机制,自身免疫,和神经退行性疾病。总的来说,我们总结了NLRP生物学的最新发现,它们形成的炎性体,以及它们在健康和疾病中的作用,并为NLRP炎性体的未来研究提供治疗策略和观点。
NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, despite their protective role, aberrant NLPR inflammasome activation and gain-of-function mutations in NLRP sensor proteins are involved in occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases. In the last few years, significant advances have been achieved in the understanding of the NLRP inflammasome physiological functions and their molecular mechanisms of activation, as well as therapeutics that target NLRP inflammasome activity in inflammatory diseases. Here, we provide the latest research progress on NLRP inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRP7, NLRP2, NLRP9, NLRP10, and NLRP12 regarding their structural and assembling features, signaling transduction and molecular activation mechanisms. Importantly, we highlight the mechanisms associated with NLRP inflammasome dysregulation involved in numerous human auto-inflammatory, autoimmune, and neurodegenerative diseases. Overall, we summarize the latest discoveries in NLRP biology, their forming inflammasomes, and their role in health and diseases, and provide therapeutic strategies and perspectives for future studies about NLRP inflammasomes.