Environmental Pollutant Tetrachloro-1,4-benzoquinone Exerts Neurotoxicity and Potential Protective Effects of...

The neurotoxicity mechanisms of tetrachloro-1,4-benzoquinone(TCBQ) remain poorly understood. This study integrated computational simulations validation to elucidate TCBQ-induced neurotoxicity.

In our investigation of the neurotoxic effects of TCBQ, we employed a diverse range of analytical techniques, including protein-protein interaction (PPI) networks, screening for target genes and protective drugs, as well as performing KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses. Additionally, we utilized advanced methodologies such as molecular docking and molecular dynamics simulations to gain deeper insights into the mechanisms underlying TCBQ's neurotoxicity. These comprehensive approaches enabled us to construct a detailed understanding of how TCBQ may contribute to neurotoxic outcomes. To further assess the potential connections between key target proteins and Alzheimer's disease, we utilized Mendelian randomization as a robust analytical strategy. This statistical method allowed us to explore the causal relationships that may exist between the identified proteins and the incidence of Alzheimer's disease, providing a clearer understanding of the biological pathways involved. For our analysis, we extracted summary-level data regarding the circulating levels of 4,907 proteins from a significant protein quantitative trait loci study conducted by the deCODE Genetics Consortium, which comprised a total of 35,559 individuals. Moreover, the outcome data for Alzheimer's disease were obtained from genome-wide association studies organized by the International Genomics of Alzheimer's Project (IGAP). This extensive research analyzed data from 17,008 participants who were diagnosed with Alzheimer's disease, alongside 37,154 control subjects, all of whom shared a European ancestry.

The results of integrated network analysis indicate that TCBQ may promote neurotoxicity through alzheimer 's disease. The main targets involved TNF, NOS2, IL6, and others. TCBQ and protective drug curcumin have a low binding score and compact complex with TNF, NOS2, IL6. 5 TNF subtype TNFSF13B, TNFRSF1B, TNFRSF13C, TNFSF12, NFRSF11B has a causal relationship with Alzheimer's disease.

TCBQ can promote neurotoxicity by increasing inflammation and alzheimer 's disease.

Our study provides a theoretical basis for the subsequent experimental study of TCBQ in neurotoxicity. TNF plays an important role in alzheimer 's disease.