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.