Investigating the mechanistic insight of environmental chemical induced neurodegeneration the insilico simulation

Abstract

Neurodegenerative diseases (NDDs) are irredeemable and incapacitating conditions that newlineresult in progressive degeneration. Associations of these problems are correlated with newlinedifferent pathological features including a major inclination towards the oxidative stress newline(OS). OS can cause cellular damage that result in cell death due to overproduction of newlinereactive oxygen species (ROS) that may play the crucial role in the disease progression. newlineAn impaired mechanism in correlation with reduced expression of antioxidant proteins newlineis the very common feature among most of the NDDs. Various in-vitro and in-vivo newlinestudies suggest the adverse effect of environmental chemicals specifically, exposure to newlinepesticides, leads to growing number of human pathological conditions; among these, newlineneurodegenerative disorders is an emerging issue nowadays. Role of Nuclear factor newlineerythroid 2 related factor 2 (Nrf2/ARE) pathway is well established in a neuroprotection newlinein concern with stress-mediated neurodegeneration. Under stress condition, it newlinecoordinates the transcription of genes involved in phase II detoxification and an newlineantioxidant defence that is used to protect the cell from oxidative stress. The current insilico study was attempted to investigate the mechanism involved in environmental newlinechemical induced neurodegeneration and to identify potential drug target using system newlinebiology approaches and to design potential drug molecule for the target through drug newlinediscovery process followed by in-vitro validation.The protein-protein interaction (PPI) newlinenetwork was build using STRING 11.0 database, based on experimental, and coexpression data with 0.007 confidence score as main parameter for analysis. Following newlinethe study, the network was visualized and analyzed using Cytoscape v 3.6.0 plug-in newlineNetwork analyzer, based on betweenness centrality (BC) and node degree as topology newlineparameter for study. The functional enrichment analysis of identified gene was done newlineusing PANTHER GENE ONTOLOGY (GO) software and Database for Annotation, newlineVisualization, and Integrated discovery Functional Annotation Tool (DAVID) tool newlinetaking statistical parameters Bonferroni correction, fold enrichment and p-value. newline