Fig. 2

cGAS activation in different CNS diseases and conditions. Activation of cGAS-STING-IFN-I signaling is a convergent pathway in various CNS diseases and conditions. In AD, the accumulation of tau tangles and amyloid plaques can lead to the activation of cGAS [46,47,48]. In PD, PINK1 and PRKN mutations and αSyn preformed fibril (αSyn-PFF) can induce cGAS activation [24, 49]. In ALS, Mutant TDP-43 protein can activate cGAS [29]. C9orf72 mutation leads to impaired degradation of STING, causing activation of the IFN-I response [50]. In Huntington’s disease (HD), cGAS activation is induced by DNA damage caused by mutant HTT protein (mHTT) [51]. In traumatic brain injury (TBI), traumatic impact induces DNA damage and neuronal death, activating cGAS by DNA released from dying neurons [52, 53]. In the context of aging and senescence, the activation of cGAS-STING is an important contributor to the development of senescence and senescence-associated secretory phenotype (SASP) [18, 54,55,56,57]