摘要
环鸟嘌呤-腺嘌呤核苷酸合成酶(cGAS)-干扰素基因刺激蛋白(STING)信号通路感知细胞质中的异常双链DNA后,诱导Ⅰ型干扰素(IFN-Ⅰ)和促炎细胞因子表达,从而激活宿主的免疫应答,增强机体抗肿瘤免疫反应和抗病原体感染。但是,cGAS-STING信号通路的持续激活会驱动自身免疫性疾病、衰老相关炎症和神经退行性病变等疾病。本文阐述了cGAS-STING信号通路参与调控多种免疫相关性疾病发生发展的机制,重点回顾了STING激动剂、cGAS抑制剂以及STING抑制剂的研发进展,为cGAS-STING调节剂的研发提供更多理论参考。
Upon monitoring cytoplasmic aberrant double-stranded DNA,cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines,which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection.However,sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases,aging-associated inflammation,and neurodegenerative pathologies.Herein,we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases,with a particular review of the research and development progress of STING agonists,cGAS inhibitors,and STING inhibitors,aiming to provide some theoretical reference for the future development of cGAS-STING modulators.
作者
娄方宁
郑明月
陈凯先
张素林
LOU Fangning;ZHENG Mingyue;CHEN Kaixian;ZHANG Sulin(School of Pharmacy,China Pharmaceutical University,Nanjing 211198;Drug Discovery and Design Center,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2024年第1期15-25,共11页
Journal of China Pharmaceutical University
基金
国家自然科学基金项目(No.T2225002,82273855)
国家重点研发计划项目(No.2022YFC3400504)
中国科学院青年创新促进会资助项目(No.2023296)
上海市自然科学基金项目(No.22ZR1474300)。