| First Author | Xie X | Year | 2023 |
| Journal | Nat Aging | Volume | 3 |
| Issue | 2 | Pages | 202-212 |
| PubMed ID | 37118112 | Mgi Jnum | J:334150 |
| Mgi Id | MGI:7447002 | Doi | 10.1038/s43587-022-00337-2 |
| Citation | Xia X, et al. (2023) Activation of innate immune cGAS_STING pathway contributes to Alzheimer's pathogenesis in 5xFAD mice. Nat Aging 3:202-212 |
| abstractText | cGAS senses microbial and host-derived double-stranded DNA in cytoplasm to trigger cellular innate immune response in a STING-dependent manner; however, it remains unknown whether the cGAS-STING pathway in innate immunity contributes to Alzheimerâs disease (AD). Here we demonstrated the detectable binding of the cGAS double-stranded DNA in cytoplasm and the activation of the microglial cGAS-STING pathway in brains of human AD and aged mice. Cgasâ/â;5ÃFAD mice were largely protected from cognitive impairment, amyloid-β pathology, neuroinflammation and other sequelae associated with AD. Furthermore, Cgas deficiency in microglia inhibited a neurotoxic A1 astrocytic phenotype and thus alleviated oligomeric amyloid-β peptide-induced neurotoxicity. Finally, administration of STING inhibitor H-151 potently suppressed the activation of the cGAS-STING pathway and ameliorated AD pathogenesis in 5ÃFAD mice. In conclusion, our present study has identified a critical molecular link between innate immunity and AD and suggests that therapeutic targeting of the cGAS-STING pathway activity might effectively interfere with the progression of AD. |
