The Abnormal ERα-miRNA Cross-Talk in AD-Affected Human Hippocampus: A Bioinformatics Perspective

Estrogen's impact on Alzheimer's disease (AD) is multifaceted, with its receptors potentially influencing AD pathology in both beneficial and detrimental ways. This study aims to dissect the intricate cross-talk between estrogen receptor alpha (ERα) and microRNAs (miRNAs) in AD-affected human hippocampus. Through a comprehensive literature review in the PubMed database, coupled with a GeneCards database search, we obtained AD-related key miRNAs and genes in the hippocampus. Using bioinformatics tools, we predicted target genes and miRNAs of ERα, and the targets of the identified miRNAs. The integration of these elements resulted in the construction of an ERα-related FFL network, which includes 13 miRNAs and 56 core genes. Gene ontology (GO) and pathway enrichment analyses were conducted, revealing significant enrichment in biological processes such as neuron death and response to metal ions, and cellular components like membrane microdomains. Notably, the AKT-associated signaling pathway was prominently highlighted, with key genes including GSK3A, CDKN1A, AKT2, and MDM2, and key miRNAs including miR-485 and let-7f, suggesting a potential role of ERα in modulating this pathway in AD. The findings of this study provide a novel perspective on the regulatory network of ERα in the hippocampal region of AD and may pave the way for future research into the therapeutic potential of targeting the ERα pathway in neurodegenerative diseases.