Exploring drug repurposing as a therapeutic strategy for non-alcoholic fatty liver disease (NAFLD): identification of potential targets and pathways.

This study investigates drug repurposing as a viable approach identifying existing pharmacological agents that could be applied to NAFLD management. Non-alcoholic fatty liver disease (NAFLD) is a prevalent and complex liver condition affecting approximately 25% of the global population, with significant links to metabolic disorders such as obesity and type 2 diabetes. Despite its high burden, no approved therapies currently exist for NAFLD, underscoring the need for effective treatments. We utilized two publicly available datasets (GSE126848 and GSE130970) to identify differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network using Cytoscape. Hub and bottleneck (H&B) genes were identified and further analyzed for pathway enrichment using DAVID and KEGG. Drug candidates were identified through the Connectivity Map (CMap) platform, focusing on compounds with counter-gene signatures. Pathway analysis highlighted critical pathways involved in NAFLD pathogenesis, including the AGE-RAGE and Rap1 signaling pathways. Several promising repurposed drugs, such as WYE-354 and Triciribine, were identified, targeting key mechanisms like lipid metabolism and inflammation. This study suggests that drug repurposing may accelerate the development of effective NAFLD therapies, although further clinical validation is needed to confirm the therapeutic potential of these findings.