SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease

doi:10.14336/AD.2023.0516-1

科研成果详情

题名	SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease
作者	Miao, Xuemeng 1,2; Wu, Qian2; Du, Siyu ; Xiang, Ludan 2; Zhou, Siyao 2; Zhu, Junzhe 3; Chen, Zirun ; Wang, Hui3; Pan, Xuyi 3; Fan, Yiren 3; Zhang, Lihan 3; Qian, Jingkang 3; Xing, Yuxuan 3; Xie, Yiyang 3; Hu, Lixin2; Xu, Haiyun2; Wang, Wei2,5; Wang, Ying 4,6; Huang, Zhihui 1,2,7
发表期刊	AGING AND DISEASE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Alzheimer's disease SARM1 degeneration inflammation memory
其他关键词	NEUROINFLAMMATION ; TNF ; ACTIVATION ; DEGENERATION ; DELETION
摘要	Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1(Nestin)-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the A beta deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-alpha (TNF-alpha) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, A beta deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-alpha pathway in AD model mice.
资助项目	Natural Science Foundation of Zhejiang Province [LR21H090001, LZ23C090001]; National Natural Science Foundation [81971172, 92049104]
出版者	INT SOC AGING & DISEASE
ISSN	2152-5250
卷号	15 期号:1 页码:390-407
DOI	10.14336/AD.2023.0516-1
页数	18
WOS类目	Geriatrics & Gerontology
WOS研究方向	Geriatrics & Gerontology
WOS记录号	WOS:000998058100001
收录类别	SCIE ; PUBMED ; SCOPUS
发表日期	2023-05-25
URL	查看原文
Pubmed记录号	37307837
Scopus记录号	2-s2.0-85180169637
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/181055
专题	精神医学学院第一临床医学院（信息与工程学院）、附属第一医院
通讯作者	Wang, Wei; Wang, Ying; Huang, Zhihui
作者单位	1.Hangzhou Normal Univ, Coll Pharm, Hangzhou 311121, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Sch Mental Hlth, Wenzhou 325035, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Sch Clin Med Sci 1, Sch Informat & Engn, Wenzhou 325205, Zhejiang, Peoples R China; 4.Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Clin Res Ctr, Sch Med, Hangzhou 310003, Zhejiang, Peoples R China; 5.Wenzhou Med Univ, Wenzhou, Zhejiang, Peoples R China; 6.Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Hangzhou, Zhejiang, Peoples R China; 7.Hangzhou Normal Univ, Hangzhou, Zhejiang, Peoples R China
第一作者单位	精神医学学院
通讯作者单位	精神医学学院; 温州医科大学
推荐引用方式 GB/T 7714	Miao, Xuemeng,Wu, Qian,Du, Siyu,et al. SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease[J]. AGING AND DISEASE,2023,15(1):390-407.
APA	Miao, Xuemeng., Wu, Qian., Du, Siyu., Xiang, Ludan., Zhou, Siyao., ... & Huang, Zhihui. (2023). SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease. AGING AND DISEASE, 15(1), 390-407.
MLA	Miao, Xuemeng,et al."SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease".AGING AND DISEASE 15.1(2023):390-407.