Assessing the Neurotoxicity of Bisphenol A Using Network Toxicology, Molecular Docking, and Molecular Dynamics Simulation

Bisphenol A (BPA) is a prevalent environmental endocrine disruptor with potential impacts to the neurological system in humans. This study used an integrated method combining network toxicology, molecular docking, and molecular dynamics simulations to explore the molecular mechanisms underlying BPA-induced neurotoxicity. We identified 255 potential neurotoxicity-related targets through the integration and comprehensive analysis of multiple data sources, including the Comparative Toxicogenomics Database (CTD), ChEMBL, STITCH, GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database. Analysis of the protein-protein interaction (PPI) network unveiled 52 core targets, among which TNF, TP53, INS, ESR1, and PTGS2 emerged as pivotal hubs in the toxicity network. Functional enrichment analysis indicated that the core targets of BPA's influence on neurotoxicity are predominantly enriched in vital signaling cascades, including inflammatory responses, pathways of neurodegeneration, MAPK signaling pathway, serotonergic synapse pathway, and pathways in cancer. Molecular docking results demonstrated that BPA exhibited stable binding interactions with core targets. Furthermore, molecular dynamics simulations provided insights into the interactions between BPA and key targets (ESR1, TNF, and TP53), supporting the potential conformational stability of these complexes. Collectively, these computational findings contribute to understanding the potential molecular mechanisms of BPA-induced neurotoxicity and are informative for generating hypotheses related to its pathogenesis.