NLRP3炎性体是一种多蛋白复合物,在调节先天免疫系统和炎症信号中起关键作用。PAMP和DAMP激活后,NLRP3寡聚化并激活半胱天冬酶-1,其启动促炎细胞因子IL-1β和IL-18的加工和释放。NLRP3是迄今为止研究最广泛的炎性小体,由于其在几种炎性疾病中的激活剂和异常激活。使用靶向NLRP3炎性体途径的小分子和生物制剂的研究已经显示出通过阻断慢性炎症治疗各种疾病病理的积极结果。在这次审查中,我们讨论了理解NLRP3机制的最新进展,它在疾病病理学中的作用,并提供了针对NLRP3途径的治疗方法及其挑战的广泛综述。
The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs and DAMPs, NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β and IL-18. NLRP3 is the most extensively studied inflammasome to date due to its array of activators and aberrant activation in several inflammatory diseases. Studies using small molecules and biologics targeting the NLRP3 inflammasome pathway have shown positive outcomes in treating various disease pathologies by blocking chronic inflammation. In this
review, we discuss the recent advances in understanding the NLRP3 mechanism, its role in disease pathology, and provide a broad
review of therapeutics discovered to target the NLRP3 pathway and their challenges.