Protein-protein interaction network analysis for the identification of novel multi-target inhibitors and target miRNAs against Alzheimer's disease.

Abstract

This study presents a strategy for extracting significant gene complexes and then provides prospective therapeutics for AD. In this research, a total of 7905 reports published from 1981 to 2022 were retrieved. Following a review of all those articles, only the genetic association studies on AD were considered. Finally, there is a list of 453 Alzheimer-related genes in our dataset for network analysis. To this end, an experimentally derived protein-protein interaction (PPI) network from the String database was utilized to extract four meaningful gene complexes functionally interconnected using Cytoscape v3.9.1 software. The acquired gene complexes were subjected to an enrichment analysis using the ClueGO v2.5.9 tool to emphasize the most significant biological processes and pathways. Afterward, extracted gene complexes were used to extract the drugs related to AD from DGI v3.0 database and introduce some new drugs which may be helpful for this disease. Finally, a comprehensive network that included every gene connected to each gene complex group as well as the drug targets for each gene has been shown. Moreover, molecular docking studies have been performed with the selected compounds to identify the interaction pattern with the respective targets. Finally, we proposed a list of 62 compounds as multi-targeted directed drug-like compounds with a degree value between 2 and 5 and 30 compounds as target-specific drug-like compounds, which have not been proclaimed as AD-related drugs in prior scientific and medical investigations. Then, new drugs were suggested that can be experimentally examined for future work. In addition to this, four bipartite networks representing each group's genes and target miRNAs were established to introduce target miRNAs by using the miRWalk v3 server.