Exploring the molecular mechanism of Parkinson's disease triggered by combined atrazine and simazine exposure

Abstract

Occupational exposure to herbicides is an important factor for the development of Parkinson's disease (PD). Atrazine (ATR) and simazine (SIM) are dopamine neurotoxins that can cause PD-like symptoms, but the mechanism is unknown. We analyzed the differentially expressed genes (DEGs) in the substantia nigra of PD patients and controls by using the PD dataset GSE20333 from the Gene Expression Omnibus (GEO) database. The potential intersectional targets of ATR and SIM combined exposure induced PD were screened by network pharmacology. The intersection targets were used for enrichment analysis and to construct protein–protein interaction networks. The binding potentials between hub targets and triazine herbicides were validated using molecular docking, and the cellular exposure models were also constructed to validate the screened results. We identified 934 genes that showed differential expression between individuals with PD and healthy controls. Using network pharmacology, we further refined our search to 151 targets of herbicides known to contribute to PD, and identified eight potential core targets: CDK2, CYCS, FOS, LCK, NTRK2, PDGFRB, PGR, and VEGFA. Finally, molecular docking and molecular biological detection results showed that ATR and SIM each exhibit strong binding affinity to CDK2, CYCS and PGR, both ATR and SIM exposure alone or in combination can affect the expression of core targets. Our study indicates that combined exposure to ATR and SIM may play a critical role in the development of PD and offers a new perspective on occupational prevention and treatment strategies.

Keywords

• Triazine herbicides
• Parkinson's disease
• Atrazine
• Simazine
• Environmental factors