Network Analysis and Molecular Mapping for Alzheimer’s Disease to Reveal the Drug Targets of Arbutin

Abstract

Abstract Alzheimer's disease (AD) is a neurodegenerative disease that causes the degradation of brain cells. AD is the most common causative factor of dementia that leads to cognitive decline and loss of independence. Cholinesterase inhibitors and N-methyl-D- aspartate (NMDA) antagonists are currently available drugs to treat AD related symptoms. Several studies have proved that arbutin is found to be beneficial in treating various diseases thereby modulating its brain targets which further helps to reduce AD’s side effects. The present research is mainly focused to study the molecular pathways and to determine the mechanism of action of arbutin to mitigate AD using a system pharmacology approach. Bioinformatics tools are explored to identify arbutin's therapeutic targets for AD, including Cytoscape for network analysis, ShinyGo for gene ontology enrichment, and AutoDock for docking molecules. In a Cytoscape network, the Maximal Clique Centrality (MCC) algorithm of the CytoHubba plugin was used to determine the top ten hub genes. Out of 411 targets for arbutin and 395 targets for AD, 37 targets were selected and shared through the data filtering process. The biological activities of these 37 genes include post-translational regulation of the phosphorus metabolic process, response to abiotic stimulus, regulation of cell population proliferation, regulation of programmed cell death and response to oxygen-containing compounds. The top 10 enriched pathways were selected for future study from 284, including AD, cancer pathways, MAPK signaling, Diabetic cardiomyopathy and proteoglycans in cancer. Our results proved that arbutin can reduce the possibility of developing AD by modulating the activity of primary pathways groups, including its pharmacological mechanism of action in AD, revealing its ten therapeutic targets.