Exploring the therapeutic potential of marine actinomycetes: a systems biology-based approach for Alzheimer’s disease treatment

Abstract Background This study addresses the urgent need for novel Alzheimer’s Disease (AD) treatments, focusing on the therapeutic potential of marine Actinomycetes compounds. Current AD therapies provide only symptomatic relief, necessitating a paradigm shift toward more effective interventions. Methodology Ninety-one bioactive compounds were methodically identified from Actinomycetes strains in the Indian Ocean. Rigorous ADME analysis and in silico toxicological screening narrowed the selection to 19 compounds, including Helquinoline, Bonactin, Azamerone, and Arcyriaflavin A. These compounds demonstrated favorable drug-like properties and activity against crucial AD targets. Utilizing network pharmacology, a bioactive-target-disease association network was constructed to unveil intricate relationships between compounds and target proteins in the context of AD. Topological analysis highlighted influential targets such as SRC, MAPK1, EGFR, PRKCA, PRKCD, and CDK2. Protein–Protein Interaction (PPI) mapping revealed interconnected pathways influenced by these compounds. Results Focus narrowed to the top 10 pathways associated with key hub–bottleneck genes. The GnRH signaling, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways exhibited remarkable fold enrichment, emphasizing their central roles in AD pathogenesis. The GnRH signaling pathway aligned with endocrine dysregulation in AD, EGFR’s dual role in prion-like propagation and amyloid-β pathology, and ErbB signaling’s multifaceted contributions. Conclusion In conclusion, this study presents marine Actinomycetes compounds as potential poly-pharmacological modulators in AD. Despite promising results, cautious optimism is warranted, requiring further experimental validation. The identified compounds and pathways offer a novel perspective, laying the groundwork for targeted interventions within the intricate landscape of AD. This research contributes to advancing AD therapeutics within a systems biology framework, introducing innovative approaches to address this complex neurodegenerative disorder.