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Published on: June 17, 2015
Exploring the Potential Targets and Protective Agents in Mercury-Induced Anxiety Disorders Using Network Toxicology,
Masoumeh Farahani1, Fatemeh Bagheri2, Mostafa Rezaei-Tavirani3
1Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Studies show that anxiety is one of the most common symptoms of mercury poisoning. The mechanism of mercury toxicity is not known in detail. This study aimed to broaden our understanding of mercury-induced anxiety and suggest potential protective agents. A list of genes associated with anxiety was extracted from the overlap between GeneCards, DisGeNET, and Diseases to decipher protein-protein interaction (PPI) and core sub-network. The comparative toxicogenomic database (CTD) helped to identify core mercury targets in anxiety disorders. Detailed interactions and relevant functions were obtained through GeneMANIA. Network pharmacology and molecular docking approaches identified potential protective agents-mercury target interactions. Among the eight proteins in the anxiety-related core sub-network (IL1B, IL6, TNF, IFNG, STAT3, TP53, EP300, and ESR1), the top-ranked proteins IL1B, IL6, TNF, and IFNG were revealed as core mercury targets with key interactions in disrupting the inflammatory responses and interfering with cellular processes. GeneMANIA highlighted the functions of CASP1, TNFAIP3, and SQSTM1 as first neighbors of the core mercury targets. Quercetin, selenium, curcumin, and glutathione were specified as factors that target the most mercury-responsive genes. Molecular docking revealed strong binding affinities between protective agents (quercetin and curcumin) and core target proteins. This study presented a network biology approach in toxicology and pharmacology to further understand the mechanism of mercury toxicity and its therapeutic solution for anxiety disorders.
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