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

Abstract

Aim: This study investigates drug repurposing as a viable approach identifying existing pharmacological agents that could be applied to NAFLD management.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.