The cGAS-STING pathway as a therapeutic target in inflammatory diseases.
The cGAS-STING pathway as a therapeutic target in inflammatory diseases.
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cGAS - STING通路作为炎症性疾病的一个治疗靶点
DOI：
10.1038/s41577-021-00524-z
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Ablasser A
中科院分区：
文献类型：
--
作者：
Decout A;Katz JD;Venkatraman S;Ablasser A
在感染、细胞应激和组织损伤的环境中，cGAS-STING信号通路已经成为炎症的关键介质。CGAS-STING途径广泛参与的基础是其感知和调节细胞对微生物和宿主来源的DNA的反应的能力，这些DNA是普遍存在的危险相关分子。对cGAS-STING通路的结构和分子生物学的深入研究使选择性小分子抑制剂的开发成为可能，这些小分子抑制剂有可能靶向cGAS-STING轴治疗一些人类炎症性疾病。在这里，我们概述了cGAS-STING信号级联的主要元件，并讨论了cGAS-STING活性与各种自体炎症、自身免疫和退行性疾病关联的一般机制。最后，我们概述了最近开发的cGAS和STING拮抗剂的化学性质，并总结了它们潜在的临床应用。CGAS-STING途径驱动先天性免疫激活，以响应胞浆DNA。这对细菌和病毒的免疫力很重要，但cGAS活性异常也与炎症性疾病有关。在这里，Ablasser和他的同事们讨论了cGAS刺痛信号如何在各种自身免疫、炎症和退行性疾病中发挥作用，并描述了针对这一途径的新疗法。
The cGAS–STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS–STING pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS–STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS–STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS–STING signalling cascade and discuss the general mechanisms underlying the association of cGAS–STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications. The cGAS–STING pathway drives innate immune activation in response to cytosolic DNA. This is important for immunity to bacteria and viruses, but aberrant cGAS–STING activity is also linked to inflammatory disease. Here, Ablasser and colleagues discuss how cGAS–STING signalling contributes to various autoimmune, inflammatory and degenerative diseases and describe the novel therapeutics targeting this pathway.
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影响因子：
64.8
作者：
通讯作者：
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染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
9.3
作者：
Abdullah A;Zhang M;Frugier T;Bedoui S;Taylor JM;Crack PJ
通讯作者：
Crack PJ
影响因子：
13.3
作者：
An, Jie;Durcan, Laura;Elkon, Keith B.
通讯作者：
Elkon, Keith B.