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Network Toxicology and Molecular Dynamics Simulation Elucidate Bisphenol A-Induced Neurotoxicity in SVGP12 Astrocytes: Mechanistic Insights and Risk Assessment for Chronic Neurodegenerative Diseases

Authors: XU Jin; CHEN Xingxing; DENG Shan; LEI Zhigang; LIU Quanhui; HUANG Ben; ZHANG Dandan

DOI: 10.7524/j.issn.0254-6108.2026030601Status: Verified Translated Edition
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Key Findings in This Report

• • Identified six key toxic proteins (TP53, HSP90AA1, HSP90AB1, INS, BCL2, AKT1) common to BPA-induced AD, PD, and HD; BCL2 is the most central hub, indicating a convergent apoptotic mechanism across diseases. • • BPA exposure induces oxidative stress and cell cycle arrest in SVGP12 astrocytes, leading to mitochondrial apoptosis via inhibition of INS-AKT1-BCL2 and activation of TP53-HSP90 pathways, disrupting neural homeostasis. • • The study integrates network toxicology, molecular docking, and molecular dynamics simulations, providing a multi-scale approach to predict and validate BPA neurotoxicity, surpassing traditional single-target analyses. • • The findings establish a mechanistic link between BPA and three major neurodegenerative diseases, offering a unified target set for therapeutic intervention and risk assessment of BPA-related neurotoxicity.