Melatonin protects mouse hippocampal neurons from neurotoxicity induced by amyloid β-peptide25–35

Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the leading cause of dementia in the elderly, as classified by the WHO. Its neuropathological hallmarks include the accumulation of amyloid-β (Aβ) plaques and intracellular tau tangles, which contribute to oxidative stress, mitochondrial dysfunction, lipid peroxidation, and neuronal death. Emerging evidence suggests that melatonin, a potent antioxidant produced by the pineal gland, plays a neuroprotective role in AD, yet its precise mechanisms remain underexplored. In this study, we utilized a physiologically relevant primary culture of hippocampal neurons to investigate melatonin’s protective effects against toxicity induced by Aβ25–35. Our findings demonstrate that melatonin significantly enhances cellular metabolism and viability while reducing reactive oxygen species (ROS) levels and lipid peroxidation, thereby mitigating Aβ-induced neurotoxicity. These results provide mechanistic insights into melatonin’s antioxidative and neuroprotective properties, reinforcing its potential as a therapeutic agent against oxidative stress in AD. This study underscores the promise of melatonin-based interventions in the development of novel antioxidant-targeted therapies for AD.