Abstract
Melatonin is a hormone released by the pineal gland that regulates the sleep-wake cycle. It has been widely studied for its therapeutic effects on Alzheimer's disease (AD), particularly through the amyloidosis, oxidative stress, and neuroinflammation pathways. Nevertheless, the mechanisms through which it exerts its neuroprotective effects in AD are still largely unknown. Data mining was used to identify potential gene targets that link melatonin's effects to AD pathways, yielding a comprehensive view of the underlying molecular mechanisms. We identified 3397 genes related to AD from DisGeNet and 329 melatonin gene targets from ChEMBL, which revealed 223 overlapping genes and the potential shared pathways. These genes were used to construct a protein-protein interaction (PPI) network comprising 143 nodes and 823 edges, which demonstrated significant PPI enrichment. A cluster analysis highlighted two key clusters centered on MMP2 and NR3C1, with both genes playing crucial roles in steroid hormone signaling, apoptosis, and monoamine neurotransmission. Gene Ontology (GO) enrichment and KEGG pathway analyses further elucidated their involvement in critical pathways, for instance, steroid hormone signaling and apoptosis regulation, significantly influencing AD pathology through mechanisms such as extracellular matrix remodeling, epigenetic modifications, and neuroinflammation. Our findings emphasize MMP2 and NR3C1 as important gene targets for future research on melatonin treatment in AD, paving the way for further investigations into their roles in AD pathophysiology.