cGAS-STING信号通路调节剂在免疫治疗中的研究进展
Research progress of cGAS-STING signaling pathway modulators in immunotherapy
娄方宁 1郑明月 2陈凯先 3张素林2
作者信息
- 1. 中国药科大学药学院, 南京 211198
- 2. 中国科学院上海药物研究所, 原创新药研究全国重点实验室,药物发现与设计中心, 上海 201203
- 3. 中国药科大学药学院, 南京 211198;中国科学院上海药物研究所, 原创新药研究全国重点实验室,药物发现与设计中心, 上海 201203
- 折叠
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.
Abstract
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.
关键词
cGAS-STING信号通路/STING激动剂/cGAS抑制剂/STING抑制剂/免疫治疗Key words
cGAS-STING signaling pathway/STING agonist/cGAS inhibitor/STING inhibitor/immunotherapy引用本文复制引用
基金项目
国家自然科学基金(T2225002)
国家自然科学基金(82273855)
国家重点研发计划项目(2022YFC3400504)
中国科学院青年创新促进会资助项目(2023296)
上海市自然科学基金(22ZR1474300)
出版年
2024
国家科技期刊平台
NSTL
万方数据