Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that triggers a type-I interferon response. When self or microbial DNA enters the cytoplasm, cGAS binds to it and catalyzes the synthesis of cGAMP. The production of type-I IFNs is then triggered by cGAMP acting as a second messenger that binds to and activates the endoplasmic reticulum protein STING. STING attracts TBK1, which phosphorylates substrates like IKK, cRel, and p62 as well as transcription factors like IRF3/7.
In Huntington disease (HD), cGAS plays a crucial role in controlling inflammatory and autophagic responses. Age-related macular degeneration and cellular senescence are two conditions that cGAS can significantly affect by inducing signaling that is known to promote the up-regulation of inflammatory genes. This shows that there is a strong molecular and signaling connection between the inflammatory response and autophagy.cGAS also plays a significant role in the regulation of autophagy.
|G150 (G-150) is a novel,potent and selective inhibitor of h-cGAS (human cyclic GMP-AMP synthase) which inhibits dsDNA-triggered interferon expression with an IC50 of 10.2 nM.
|RU.521 (RU320521) is a novel and selective cyclic GMP-AMP synthase (cGAS) inhibitor with potential usefulness for autoimmune diseases.