Selected genes from insulin resistance pathway.

Insulin resistance (IR) and Alzheimer’s disease (AD) share overlapping molecular mechanisms, but the precise link between these conditions remains unclear. MicroRNAs, as post-transcriptional regulators of gene expression, may mediate this connection by targeting genes involved in both pathways. In this study, we employed a multi-step bioinformatics approach to identify microRNAs that simultaneously regulate genes associated with IR and AD. Twenty key IR-related genes were selected from the literature, and their microRNA regulators were predicted using five computational tools. These predictions were validated using experimentally supported databases (TarBase and miRTarBase), and each miRNA–gene interaction was scored. Sixteen high-confidence microRNAs were shortlisted based on cumulative prediction and validation scores. These microRNAs were then analyzed for their interactions with AD pathway genes via KEGG pathway analysis. The AD-related target genes were further processed through protein–protein interaction network analysis using STRING and hub gene identification via Cytoscape. Functional enrichment of these hub genes using Gene Ontology and KEGG analysis revealed their involvement in shared biological processes, including apoptosis, insulin signaling, glucose metabolism, and neuroinflammation. Prominent candidates such as miR-7-5p, miR-106b, miR-424-5p, and miR-15a were identified. These results suggest that a subset of microRNAs may serve as critical molecular links between IR and AD, offering potential targets for early diagnosis and intervention.胰岛素抵抗（Insulin resistance, IR）与阿尔茨海默病（Alzheimer’s disease, AD）存在重叠的分子机制，但二者间的确切关联仍未明确。微小RNA（microRNAs, miRNAs）作为基因表达的转录后调控因子，可通过靶向两种疾病通路中共有的基因来介导这一关联。本研究采用多步骤生物信息学方法，筛选可同时调控与IR和AD相关基因的微小RNA。首先从已发表文献中选取20个关键IR相关基因，利用5种计算工具预测其微小RNA调控靶点；随后通过实验验证数据库TarBase与miRTarBase对上述预测结果进行验证，并对每一组miRNA-基因互作对进行评分。基于累积的预测与验证得分，最终筛选出16个高可信度微小RNA。随后通过KEGG通路分析，探究这些微小RNA与AD通路基因的互作关系。对于AD相关靶基因，进一步借助STRING构建蛋白质-蛋白质互作网络，并通过Cytoscape完成核心基因（hub gene）的鉴定。采用基因本体（Gene Ontology, GO）与KEGG分析对这些核心基因开展功能富集分析，结果显示其参与了细胞凋亡、胰岛素信号通路、葡萄糖代谢及神经炎症等共通生物学过程。最终筛选出miR-7-5p、miR-106b、miR-424-5p及miR-15a等重点候选分子。本研究结果表明，一类微小RNA可作为IR与AD之间的关键分子关联因子，为两种疾病的早期诊断及干预靶点开发提供了潜在方向。