The cGAS-STING pathway as a therapeutic target in inflammatory diseases.

TLDR: The cGAS-STING pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage as discussed by the authors, which has enabled the development of selective small-molecule inhibitors with the potential to target the CGS-STing axis in a number of inflammatory diseases.

Abstract: 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