Activation of innate immune cGAS-STING pathway contributes to Alzheimer's pathogenesis in 5xFAD mice

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	Activation of innate immune cGAS-STING pathway contributes to Alzheimer's pathogenesis in 5xFAD mice
	Xie, XC; Ma, GQ; Li, XH; Zhao, JB; Zhao, Z; Zeng, JX
	2023
发表期刊	NATURE AGING
卷号	3 期号:2 页码:202+
摘要	Xie et al. identify activation of the innate immune cGAS-STING pathway in human Alzheimer's disease (AD) brain and 5xFAD mouse model of AD. Suppressing the cGAS-STING pathway is shown as a target to alleviate AD-associated pathogenesis in mice. 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(-/-);5xFAD 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 5xFAD 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.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14388
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Xie, XC,Ma, GQ,Li, XH,et al. Activation of innate immune cGAS-STING pathway contributes to Alzheimer's pathogenesis in 5xFAD mice[J]. NATURE AGING,2023,3(2):202+.
APA	Xie, XC,Ma, GQ,Li, XH,Zhao, JB,Zhao, Z,&Zeng, JX.(2023).Activation of innate immune cGAS-STING pathway contributes to Alzheimer's pathogenesis in 5xFAD mice.NATURE AGING,3(2),202+.
MLA	Xie, XC,et al."Activation of innate immune cGAS-STING pathway contributes to Alzheimer's pathogenesis in 5xFAD mice".NATURE AGING 3.2(2023):202+.

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