Discovery of Potential Drug Targeting Key Genes in Alzheimer’s Disease: Insights from Transcriptome Analysis and Molecular Docking

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2024-05-27 DOI:10.1007/s12031-024-02208-4

Hanjie Liu, Hui Yang, Maochun You, Siyu Zhang, Sihan Huang, Xin Tan, Qi Liu, Cen Jiang, Lushuang Xie

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Abstract

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder that presents a significant global health challenge. To explore drugs targeting key genes in AD, R software was used to analyze the data of single nuclei transcriptome from human cerebral frontal cortex in AD, and the differentially expressed genes (DEGs) were screened. Then the gene ontology (GO) analysis, Kyoto gene and genome encyclopedia (KEGG) pathway enrichment and protein-protein interaction (PPI) network were analyzed. The hub genes were calculated by Cytoscape software. Molecular docking and molecular dynamics simulation were used to evaluate and visualize the binding between candidate drugs and key genes. A total of 564 DEGs were screened, and the hub genes were ISG15, STAT1, MX1, IFIT3, IFIT2, RSAD2, IFIT1, IFI44, IFI44L and DDX58. Enrichment terms mainly included response to virus, IFN-γ signaling pathway and virus infection. Diclofenac had good binding effect with IFI44 and IFI44L. Potential drugs may act on key gene targets and then regulate biological pathways such as virus response and IFN-γ-mediated signal pathway, so as to achieve anti-virus, improve immune balance and reduce inflammatory response, and thus play a role in anti-AD.

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发现针对阿尔茨海默病关键基因的潜在药物：转录组分析和分子对接的启示。

阿尔茨海默病（AD）是一种常见的神经退行性疾病，对全球健康构成重大挑战。为了探索针对AD关键基因的药物，研究人员使用R软件分析了AD患者大脑额叶皮层单核转录组数据，筛选出差异表达基因（DEGs）。然后分析了基因本体（GO）分析、京都基因和基因组百科全书（KEGG）通路富集和蛋白相互作用（PPI）网络。中心基因由 Cytoscape 软件计算得出。分子对接和分子动力学模拟用于评估候选药物与关键基因之间的结合并使其可视化。共筛选出 564 个 DEGs，其中枢纽基因包括 ISG15、STAT1、MX1、IFIT3、IFIT2、RSAD2、IFIT1、IFI44、IFI44L 和 DDX58。富集项主要包括对病毒的反应、IFN-γ 信号通路和病毒感染。双氯芬酸与 IFI44 和 IFI44L 有很好的结合效果。潜在药物可能作用于关键基因靶点，进而调控病毒应答和IFN-γ介导的信号通路等生物通路，达到抗病毒、改善免疫平衡和减轻炎症反应的目的，从而在抗AD中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.