Network Toxicology and Molecular Docking Strategy for Analyzing the Toxicity and Mechanisms of Bisphenol A in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder marked by memory deterioration and cognitive impairment. Bisphenol A (BPA), a common environmental pollutant, has been linked to neurotoxicity and may contribute to AD development. This study aims to uncover potential toxicological targets and molecular mechanisms of BPA-induced AD. BPA's potential neurotoxic effects were predicted using ProTox and ADMETlab. Target prediction for BPA was conducted through the STITCH and Swiss Target Prediction platforms, while AD-related targets were compiled from GeneCards, OMIM, and the Therapeutic Target Database (TTD). Protein-protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Molecular docking was employed to evaluate the binding interactions between BPA and the identified core targets. Through systematic bioinformatics analyses, 137 candidate targets for BPA-elicited AD were identified. Screening via PPI network analysis highlighted five key targets: STAT3, AKT1, INS, EGFR, and PTEN. GO and KEGG pathway enrichment revealed significant involvement in oxidative stress, neuronal apoptosis, neurodegenerative processes, and pathways such as PI3K/AKT, MAPK, lipid and atherosclerosis, and AD signaling. Molecular docking simulations confirmed strong binding affinities between BPA and these core targets. This study sheds light on the molecular mechanisms underlying BPA's neurotoxic effects in the context of AD and provides a foundation for further research into preventive and therapeutic strategies. The integration of network toxicology and molecular docking offers a robust framework for unraveling toxic pathways of uncharacterized environmental and chemical agents.