Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

Abstract

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.

Keywords: gene–drug interaction; hub gene; protein–protein interaction (PPI); systems biology; vascular dementia.