Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive impairment, loss of motor function, widespread synaptic loss and neuronal damage and loss. Currently available treatments remain symptomatic and  effective disease-modifying therapies remain limited. 

Drug repurposing has emerged as a promising strategy for identifying new therapeutic applications of already existing drugs. Metformin, a widely prescribed antihyperglycemic agent, has demonstrated neuroprotective, anti-inflammatory, and antioxidant properties, which makes it a potential candidate for Alzheimer's treatment. The present study uses an integrated computational approach with network pharmacology and molecular docking to investigate the therapeutic potential of metformin in Alzheimer's disease treatment.

Potential metformin targets and Alzheimer's disease-associated genes were identified from publicly available databases, and overlapping targets were used to construct a protein-protein interaction network. Further, Gene Ontology (GO), and KEGG pathway enrichment analyses were carried out. Hub genes were identified based on network centrality and topology and selected for molecular docking studies to evaluate the binding affinity of metformin. Functional enrichment analysis indicated that the identified protein targets were mainly involved in inflammatory signalling, oxidative stress, apoptotic regulation, and metabolism, highlighting the multi-target function of metformin.

Docking analysis demonstrated favourable interactions between metformin and hub proteins, i.e. angiotensin-converting enzyme (ACE), moderate interactions were observed with MAPK1 and acetylcholinesterase (a primary target for current treatments). In contrast, SIRT1 exhibited comparatively weak binding, suggesting that its reported neuroprotective effects may be mediated through indirect signalling pathways rather than direct binding. 

Overall, the findings suggest that metformin functions as a multi-target therapeutic agent capable of modulating several interconnected molecular targets and biological pathways relevant to Alzheimer's disease. Although further molecular dynamics simulations and experimental validation are required, this study provides computational evidence supporting the potential repurposing of metformin as a candidate therapeutic agent for Alzheimer's disease.