Melatonin Antioxidative Defense: Therapeutical Implications for Aging and Neurodegenerative Processes

Abstract

The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal neuromodulation and vasomotor responses. It scavenges hydroxyl, carbonate and various organic radicals as well as a number of reactive nitrogen species. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. Melatonin preserves mitochondrial homeostasis, reduces free radical generation and protects mitochondrial ATP synthesis by stimulating Complex I and IV activities. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases. The efficacy of melatonin in preventing oxidative damage in either cultured neuronal cells or in the brains of animals treated with various neurotoxic agents, suggests that melatonin has a potential therapeutic value as a neuroprotective drug in treatment of Alzheimer´s disease (AD), Parkinson´s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington´s disease (HD), stroke and brain trauma. Therapeutic trials with melatonin indicate that it has a potential therapeutic value as a neuroprotective drug in treatment of AD, ALS and HD. In the case of other neurological conditions, like PD, the evidence is less compelling. Melatonin's efficacy in combating free radical damage in the brain suggests that it can be a valuable therapeutic agent in the treatment of cerebral edema following traumatic brain injury or stroke. Clinical trials employing melatonin doses in the range of 50-100 mg/day are warranted before its relative merits as a neuroprotective agent is definitively established.

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“…An aspect of particular relevance to aging as well as to chronic age-related diseases concerns Nrf2-mediated protection against oxidative stress, which is typically associated with senescence [15,88]. These findings are well in accordance with similar effects observed with melatonin [52,[90][91][92][93]. An additional complication results from the negative relationship between Nrf2 and NF-κB, which is correspondingly modulated by melatonin in terms of reducing NF-κB activity [15].…”

“…Mitochondrial dysfunction and the development of a proinflammatory phenotype represent major sources of free radical generation and cause an age-related, persistent low-grade oxidative stress, in which melatonin has been shown to be beneficial [52,92,93,122,123]. Low chronic oxidative stress was also shown to affect telomere length, especially via formation of 8-oxodG in the telomeric sequence TTAGGG [92,124,125].…”

Brain nutrition-orthomolecular aspects

“…[83]. Melatonin is a powerful free radical scavenger antioxidant that ameliorates the mitochondrial energetic physiology in order to be neuroprotective, including against the beta-amyloid peptide [Aβ] damaging [84][85][86][87]. Melatonin prescription increases the hippocampal, neuronal and dendritic precursor cell development, differentiation, maturation and survival [88,89].…”

Influence chronopharmacology therapy methionine (melaxen) on the dynamics of sleep disturbance, cognitive and emotional disorders, brain-derived neurotrophic factor (BDNF) in patients with cerebral stroke in the early and late recovery periods

“…Также мелатонин оказывает свое защитное действие после ишемии через никотиновые а7-субъединицы ре-цептора ацетилхолина [17]. Клинические испытания, ис-пользующие дозы мелатонина в диапазоне 50-100 мг/ сут, установили его нейропротективный эффект [18].…”