Therapeutic Multifaceted Potential of Melatonin in Neurodegenerative Diseases: From Neuroprotective Mechanisms to Translational Promise

Abstract:

Neurodegenerative diseases, primarily characterized by progressive motor dysfunctions and debilitating memory impairments, have increasingly emerged as a major challenge in public health worldwide. The development of effective neuroprotective agents remains an urgent goal to halt the progression of neurodegenerative disorders. These agents target multiple interconnected pathological pathways, including neuroinflammation, mitochondrial dysfunction, autophagy dysregulation, apoptotic cell death, pathological protein aggregation, and sustained oxidative stress. Accumulating evidence from preclinical studies suggests that melatonin, a neurohormone synthesized by the pineal gland, possesses considerable neuroprotective potential. This effect is mediated by its ability to modulate various pathophysiological processes and intracellular signaling cascades that are commonly disrupted in neurodegenerative conditions. Melatonin's pleiotropic actions, including its potent antioxidant, anti-inflammatory, and anti-apoptotic properties, make it a promising candidate for therapeutic intervention. The present review provides a comprehensive overview of the therapeutic potential of melatonin across major neurodegenerative disorders, including Alzheimer's Disease (AD), Vascular Dementia (VD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Traumatic Brain Injury (TBI), and Huntington's Disease (HD), with discussion of its roles and underlying mechanisms in each condition. Future research should prioritize well-designed clinical trials and improved formulation strategies to establish melatonin's efficacy and safety. By summarizing the current state of knowledge and identifying translational gaps, this review highlights both the therapeutic promise of melatonin and the critical steps needed to realize its potential in clinical practice.