| 论文题目: | Activation of Innate Immune cGAS-STING Pathway Contributes to Alzheimer's Pathogenesis in 5×FAD Mice |
| 作者: | Xie, Xiaochun; Ma, Guanqin; Li, Xiaohong; Zhao, Jiebin; Zhao, Zhen; Zeng, Jianxiong |
| 联系作者: | zengjianxiong@mail.kiz.ac.cn |
| 发表年度: | 2023 |
| DOI: | doi: 10.1038/s43587-022-00337-2 |
| 摘要: | 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 Alzheimer's 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. Cgas-/-;5*FAD mice were largely protected from cognitive impairment, amyloid-beta pathology, neuroinflammation and other sequelae associated with AD. Furthermore, Cgas deficiency in microglia inhibited a neurotoxic A1 astrocytic phenotype and thus alleviated oligomeric amyloid-beta peptide-induced neurotoxicity. Finally, administration of STING inhibitor H-151 potently suppressed the activation of the cGAS-STING pathway and ameliorated AD pathogenesis in 5*FAD 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 |
| 刊物名称: | Nature Aging |
| 论文出处: | https://www.nature.com/articles/s43587-022-00337-2 |
| 影响因子: | 16.6(2022IF) |
