Table_5_Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses.XLSX

Vascular dementia (VaD) is considered to be the second most common form of dementia after Alzheimer’s disease, and no specific drugs have been approved for VaD treatment. We aimed to identify shared transcriptomic signatures between the frontal cortex and temporal cortex in VaD by bioinformatics analyses. Gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) and hub gene identification, hub gene–transcription factor interaction, hub gene–microRNA interaction, and hub gene–drug interaction analyses were performed. We identified 159 overlapping differentially expressed genes (DEGs) between the frontal cortex and temporal cortex that were enriched mainly in inflammation and innate immunity, synapse pruning, regeneration, positive regulation of angiogenesis, response to nutrient levels, and positive regulation of the digestive system process. We identified 10 hub genes in the PPI network (GNG13, CD163, C1QA, TLR2, SST, C1QB, ITGB2, CCR5, CRH, and TAC1), four central regulatory transcription factors (FOXC1, CREB1, GATA2, and HINFP), and four microRNAs (miR-27a-3p, miR-146a-5p, miR-335-5p, and miR-129-2-3p). Hub gene–drug interaction analysis found four drugs (maraviroc, cenicriviroc, PF-04634817, and efalizumab) that could be potential drugs for VaD treatment. Together, our results may contribute to understanding the underlying mechanisms in VaD and provide potential targets and drugs for therapeutic intervention.

血管性痴呆（Vascular dementia, VaD）被认为是仅次于阿尔茨海默病的第二大常见痴呆类型，目前尚无获批用于VaD治疗的特异性药物。本研究旨在通过生物信息学分析，明确VaD患者额叶皮层与颞叶皮层共有的转录组特征。研究开展了基因本体论（Gene Ontology, GO）富集分析、通路富集分析、蛋白质-蛋白质相互作用（Protein-Protein Interaction, PPI）网络构建与核心基因筛选、核心基因-转录因子调控互作分析、核心基因-微小RNA（microRNA, miRNA）互作分析以及核心基因-药物互作分析。本研究共筛选得到159个在额叶皮层与颞叶皮层中均存在差异表达的共同差异表达基因（differentially expressed genes, DEGs），这些基因主要富集于炎症与固有免疫、突触修剪、再生、血管生成正调控、营养水平应答以及消化系统过程正调控等生物学过程。本研究在PPI网络中筛选得到10个核心基因，分别为GNG13、CD163、C1QA、TLR2、SST、C1QB、ITGB2、CCR5、CRH及TAC1；同时鉴定出4个核心调控转录因子，即FOXC1、CREB1、GATA2与HINFP，以及4个微小RNA：miR-27a-3p、miR-146a-5p、miR-335-5p与miR-129-2-3p。核心基因-药物互作分析筛选得到4种潜在的VaD治疗药物，分别为马拉韦罗（maraviroc）、塞尼昔罗（cenicriviroc）、PF-04634817及依法珠单抗（efalizumab）。综上，本研究结果有助于阐明VaD的潜在发病机制，并为其治疗干预提供潜在的靶点与候选药物。