Exploring the phthalates-induced neurotoxicity mechanisms of neurodegenerative diseases via network toxicology, single-cell transcriptomics and molecular dynamic simulation - PubMed
3 days ago
- #Phthalates
- #Neurotoxicity
- #Neurodegenerative Diseases
- Phthalates are neurotoxicants widely used in construction, packaging, and medical products.
- Network toxicology identified 10 phthalates affecting the blood-brain barrier (BBB), with DEHP and DiBP showing neurotoxicity, immunotoxicity, and ecotoxicity.
- Phthalates may contribute to Parkinson's disease (PD), Lewy body disease (LBD), and Alzheimer's disease (AD) via apoptosis and neuroinflammatory pathways like PI3K-Akt and JAK-STAT.
- Key genes identified include BCL2, BCL2L1, IL6, IL10, and CCND1, with BCL2 in astrocytes playing a critical role in neurotoxicity.
- Molecular docking showed stable interactions between phthalates and BCL2, with DEHP and its metabolite MEHP reducing BCL2 levels and promoting pro-inflammatory astrocyte transformation.
- The study provides insights into environmental pollutants' neurotoxic effects, aiding neurodegenerative disease prevention and treatment.