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阿尔茨海默病中小胶质细胞介导的神经炎症中鼠干扰素基因的全基因组鉴定。

Genome-wide identification of murine interferon genes in microglial-mediated neuroinflammation in Alzheimer's disease.

机构信息

Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.

Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.

出版信息

J Neuroimmunol. 2023 Feb 15;375:578031. doi: 10.1016/j.jneuroim.2023.578031. Epub 2023 Jan 21.

Abstract

Interferons play a major role in microglial-mediated neuroinflammation in Alzheimer's disease (AD). We investigated the interferon transcriptome (AD versus non-AD) using N9 and murine microglia. We identified 64 interferon-related differentially expressed genes (DEG) in LPS-stimulated N9 microglia versus control cells, 26 DEG in microglia from 5XFAD versus wild-type mice, with 13 DEG common to both datasets. Network analyses identified potential key mediators (Cxcl10, Ifit3) of the interferon response in AD. Gene-drug interaction analysis identified therapeutics targeting interferon-related genes. These data characterize the microglial interferon response in AD, providing new targets and therapeutics directed towards interferon-related neuroinflammation in AD.

摘要

干扰素在阿尔茨海默病(AD)中的小胶质细胞介导的神经炎症中发挥重要作用。我们使用 N9 和小鼠小胶质细胞研究了干扰素转录组(AD 与非 AD)。我们在 LPS 刺激的 N9 小胶质细胞与对照细胞中鉴定出 64 个干扰素相关差异表达基因(DEG),在 5XFAD 小鼠与野生型小鼠的小胶质细胞中鉴定出 26 个 DEG,两个数据集共有 13 个 DEG。网络分析确定了 AD 中干扰素反应的潜在关键介质(Cxcl10、Ifit3)。基因-药物相互作用分析确定了针对干扰素相关基因的治疗方法。这些数据描述了 AD 中小胶质细胞的干扰素反应,为针对 AD 中与干扰素相关的神经炎症的新靶点和治疗方法提供了信息。

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