Blevins Hallie M, Xu Yiming, Biby Savannah, Zhang Shijun
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United States.
Front Aging Neurosci. 2022 Jun 10;14:879021. doi: 10.3389/fnagi.2022.879021. eCollection 2022.
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.
NLRP3炎性小体是一种多蛋白复合物,在调节先天性免疫系统和炎症信号传导中起关键作用。在被病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs)激活后,NLRP3发生寡聚化并激活半胱天冬酶-1,后者启动促炎细胞因子IL-1β和IL-18的加工和释放。由于其一系列激活剂以及在多种炎症性疾病中的异常激活,NLRP3是迄今为止研究最为广泛的炎性小体。使用靶向NLRP3炎性小体途径的小分子和生物制剂的研究表明,通过阻断慢性炎症,在治疗各种疾病病理方面取得了积极成果。在本综述中,我们讨论了在理解NLRP3机制及其在疾病病理中的作用方面的最新进展,并对已发现的靶向NLRP3途径的治疗方法及其挑战进行了广泛综述。