Melatonin: A Potential Anti-Oxidant Therapeutic Agent for Mitochondrial Dysfunctions and Related Disorders

Jun 19, 2015Rejuvenation research

Melatonin as a Possible Antioxidant Treatment for Mitochondrial Problems and Related Disorders

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Melatonin may protect against oxidative stress-induced mitochondrial dysfunction linked to neurodegenerative diseases.

Mitochondria are essential for energy metabolism and various cellular functions, including the regulation of reactive oxygen species (ROS) and apoptosis.
Increased ROS generation and impaired mitochondrial function are associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease.
Melatonin, a hormone produced by the pineal gland, acts as an antioxidant and selectively targets mitochondrial membranes.
Experimental models show that melatonin has a protective role in preventing mitochondrial dysfunction due to oxidative stress in neurodegenerative conditions.
The article reviews melatonin's mechanisms of action and explores potential therapeutic applications for treating mitochondrial diseases.

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Mitochondria play a central role in cellular physiology. Besides their classic function of energy metabolism, mitochondria are involved in multiple cell functions, including energy distribution through the cell, energy/heat modulation, regulation of reactive oxygen species (ROS), calcium homeostasis, and control of apoptosis. Simultaneously, mitochondria are the main producer and target of ROS with the result that multiple mitochondrial diseases are related to ROS-induced mitochondrial injuries. Increased free radical generation, enhanced mitochondrial inducible nitric oxide synthase (iNOS) activity, enhanced nitric oxide (NO) production, decreased respiratory complex activity, impaired electron transport system, and opening of mitochondrial permeability transition pores have all been suggested as factors responsible for impaired mitochondrial function. Because of these, neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and aging, are caused by ROS-induced mitochondrial dysfunctions. Melatonin, the major hormone of the pineal gland, also acts as an anti-oxidant and as a regulator of mitochondrial bioenergetic function. Melatonin is selectively taken up by mitochondrial membranes, a function not shared by other anti-oxidants, and thus has emerged as a major potential therapeutic tool for treating neurodegenerative disorders. Multiple in vitro and in vivo experiments have shown the protective role of melatonin for preventing oxidative stress-induced mitochondrial dysfunction seen in experimental models of PD, AD, and HD. With these functions in mind, this article reviews the protective role of melatonin with mechanistic insights against mitochondrial diseases and suggests new avenues for safe and effective treatment modalities against these devastating neurodegenerative diseases. Future insights are also discussed.

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Melatonin: A Potential Anti-Oxidant Therapeutic Agent for Mitochondrial Dysfunctions and Related Disorders

Abstract

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