Melatonin: Novel Insights in the Treatment of Neurodegenerative Diseases

Melatonin, a hormone primarily synthesized by the pineal gland and known for regulating sleep-wake cycles, has emerged as a promising therapeutic agent in neurodegenerative diseases. Recent research has uncovered novel insights into melatonin's neuroprotective effects, including its ability to modulate mitochondrial function, enhance autophagy, and regulate epigenetic mechanisms, offering new therapeutic avenues. This review summarizes current knowledge, novel mechanisms, and future research directions of melatonin in neurodegenerative diseases. This review synthesizes evidence from clinical trials and preclinical research published between 1960 and March 2025, sourced from PubMed, Scopus, Google Scholar, and the Cochrane Library. Findings highlight melatonin's potent antioxidant and anti-inflammatory properties, which mitigate oxidative stress, reduce neuroinflammation, and promote neuronal survival. Additionally, melatonin supplementation has shown promise in improving sleep disturbances, cognitive function, and quality of life in neurodegenerative diseases. Emerging evidence also suggests synergistic effects of melatonin with other neuroprotective agents and its potential in early-stage disease intervention. Despite these advances, challenges remain, including optimizing dosing regimens and understanding long-term effects. By integrating preclinical and clinical insights, this review underscores melatonin's potential as a multifaceted therapeutic agent in neurodegenerative diseases.