Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase

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	Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase
	Zhao, M; Ma, GQ; Yan, XX; Li, XH; Wang, ER; Xu, XX; Zhao, JB; Ma, XL; Zeng, JX
	2024
发表期刊	MOL PSYCHIATR
ISSN	1359-4184
卷号	29 期号:5 页码:1491-1500
摘要	Microbial infection as a type of environmental risk factors is considered to be associated with long-term increased risk of dementia, including Alzheimer's disease (AD). AD is characterized by two neuropathologically molecular hallmarks of hyperphosphorylated tau and amyloid-beta (A beta), the latter generated by several biochemically reactive enzymes, including gamma-secretase. However, how infectious risk factors contribute to pathological development of the AD core molecules remains to be addressed. In this work, we utilized a modified herpes simplex virus type 1 (mHSV-1) and found that its hippocampal infection locally promotes A beta pathology in 5 x FAD mice, the commonly used amyloid model. Mechanistically, we identified HSV-1 membrane glycoprotein US7 (Envelope gI) that interacts with and modulates gamma-secretase and consequently facilitates A beta production. Furthermore, we presented evidence that adenovirus-associated virus-mediated locally hippocampal overexpression of the US7 aggravates A beta pathology in 5 x FAD mice. Collectively, these findings identify a herpesviral factor regulating gamma-secretase in the development and progression of AD and represent a causal molecular link between infectious pathogens and neurodegeneration.
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/152453/14691
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Zhao, M,Ma, GQ,Yan, XX,et al. Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase[J]. MOL PSYCHIATR,2024,29(5):1491-1500.
APA	Zhao, M.,Ma, GQ.,Yan, XX.,Li, XH.,Wang, ER.,...&Zeng, JX.(2024).Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase.MOL PSYCHIATR,29(5),1491-1500.
MLA	Zhao, M,et al."Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase".MOL PSYCHIATR 29.5(2024):1491-1500.

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ZJX2025042102.pdf（3892KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文