神经炎症
神经退行性变
海马结构
海马体
条件基因敲除
神经科学
基因剔除小鼠
发病机制
肿瘤坏死因子α
渗透(HVAC)
中枢神经系统
氧化应激
医学
促炎细胞因子
认知功能衰退
炎症
生物
疾病
受体
病理
免疫学
痴呆
内分泌学
内科学
基因
表型
物理
热力学
生物化学
作者
Xuemeng Miao,Wei Qian,Siyu Du,Ludan Xiang,Siyao Zhou,Junzhe Zhu,Z.-G. Chen,Hui Wang,Xuyi Pan,Yiren Fan,Lihan Zhang,Jinsheng Qian,Yuxuan Xing,Yuantao Xie,Li‐Xin Hu,Haiyun Xu,Wei Wang,Y Wang,Zhihui Huang
标识
DOI:10.14336/ad.2023.0516-1
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, SARM1Nestin-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aβ 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-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, Aβ deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.
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