NLRP3炎性小体激活机制及小分子抑制剂研究进展

Research Progress of NLRP3 Inflammasome Activation Mechanism and Small Molecule Inhibitors

核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎性小体是一种多聚体蛋白复合物,可致半胱氨酸天冬氨酸蛋白酶1(cysteine asparate protease-1,caspase-1)活化,从而进一步诱导白介素(interleukin,IL)-1β和IL-18的成熟。NLRP3炎性小体是先天免疫系统抗感染的重要防线,但其过度活化与痛风、动脉粥样硬化、人类炎症性肠病、2型糖尿病、阿尔兹海默病等多种常见疾病有密切关系,因此NLRP3炎性小体是开发下一代治疗药物的新靶点。本文就近年来NLRP3炎性小体激活机制及抑制剂的研究进展进行综述,希望为相关药物研发提供新思路。

Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is a multimeric protein complex that can cause the activation of cysteine asparate protease-1(caspase-1)further induces the maturation of interleukin(IL)-1βand IL-18.NLRP3 inflammasome is an important defense line of the innate immune system against infection,but its over-activation is closely related to many common diseases such as gout,atherosclerosis,human inflammatory bowel disease,type 2 diabetes,Alzheimer's disease,etc.Therefore,the NLRP3 inflammasome is a new target for the development of next-generation therapeutic drugs.In this paper,the recent research progress of NLRP3 inflammasome activation mechanism and inhibitors was reviewed,hoping to provide new ideas for related drug research and development.