Molecular docking and proteomics approaches for the identification of neuroprotective effects of IL15.5 peptide against oxidative stress-induced apoptosis in SH-SY5Y neurons

[Display omitted] •IL15.5 targets Aβ42 aggregation, which is crucial for Alzheimer’s therapy, with evidence from proteomic analyses.•IL15.5 exhibits antioxidant activity and inhibits acetylcholinesterase.•IL15.5 protects SH-SY5Y cells from oxidative stress and apoptosis.•Modulation of the ubiquitin–proteasome system is associated with IL15.5-induced neuroprotection. Amyloid-β (Aβ) aggregation is central to Alzheimer’s disease (AD), causing oxidative and synaptic damage. We developed IL15.5, a peptide-base inhibitor derived from IL15, a natural peptide from Siamese crocodile hemoglobin. Computational and molecular assays confirm IL15.5 effectively inhibits Aβ42 aggregation, evident in thioflavin T assay results. IL15.5 also demonstrates acetylcholinesterase inhibition and antioxidant activity. It protects SH-SY5Y cells from oxidative stress and apoptosis, influencing caspase 3/MAPK pathways. Proteomic analysis reveals the role of IL15.5 in oxidative stress mitigation, affecting proteins linked to DNA repair, inflammation, and cell migration, with a significant association with Ubiquitin C. These findings suggest the potential of IL15.5 as an anti-amyloidogenic agent for AD treatment, offering neuronal protection and highlighting its therapeutic promise.