Melatonin Redox Activity. Its Potential Clinical Applications in Neurodegenerative Disorders

Abstract

Neurodegeneration is the hallmark of many chronic progressive neurogical disorders characterized by specific clinical, morphological and biochemical features. Central nervous system is very sensitive to oxidative stress, which is considered as a key factor of neurodegenerative disorders. Therefore, many therapeutical strategies are focused on molecules with redox activity to re-establish the equilibrium between pro and antioxidants. Due to the fact that melatonin readily crosses the blood- brain-barrier, concomitant with its safety profile at the highest dosages makes this dietary supplement very useful in possible clinical application in neurodegeneration. Melatonin is currently marketed in several countries as a dietary supplement with no prescription. Clinical trials have shown different effectiveness of melatonin supplementation in several disorders, including neurodegenerative disorders. Melatonin has unique biochemical properties such as scavenging of hydroxyl, carbonate, alkoxyl, peroxyl and aryl cation radicals and stimulation of activities main antioxidative enzymes (glutathione peroxidase, superoxide dismutase etc.). Moreover, it can suppress nitric oxide synthase. The present paper highlighted the potential clinical role of melatonin in main neurodegenerative diseases including Alzheimer disease, Parkinson disease, amylotrophic lateral sclerosis and multiple sclerosis. Moreover, in this review the main molecular aspects of melatonin in brain cell protection and survival mechanisms were discussed. Therefore, melatonin is regarded as a potential therapeutical agent in clinical application in neurodegenerative disorders, but this findings needs to be confirmed by the larger, more well-designed clinical trials.

Melatonin rhythms in renal transplant recipients with sleep–wake disturbances

“…It has been suggested that melatonin supplementation is beneficial in neurodegenerative disorders, by protecting brain cells from oxidative stress (Miller et al, 2015). These results are promising in view that transplanted kidneys are prone to oxidative stress-mediated injury by pre-transplant and posttransplant conditions that cause reperfusion injury or imbalance between oxidants and antioxidants (Nafar et al, 2011).…”

Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus

“…It also has anti-oxidative, anti-inflammatory, free radical scavenger, anti-aging, and neuroprotective effects, which have been connected with the redox status of cells and tissues, thus suggesting its potential clinical role in various neurodegenerative diseases [22-24, 43]. Recently, it has been proposed that melatonin promotes irradiation-induced inhibition of neurogenesis [29, 44] and proliferation, and differentiation of neural stem cells during hypoxia [45].…”

“…In a few earlier studies with infantile rats, some exogenous chemicals, such as decorin and memantine as potential neuroprotective agents, were tested for a reduction of cytopathological changes in the hippocampus due to kaolin-induced hydrocephalus [20, 21]. However, the possible roles of endogenous chemicals such as melatonin in patients with dilated ventricles and cognitive impairment have not been completely understood yet, although they could have antioxidant, free radical scavenger, and neuroprotective effects in many disorders of the body [22-24]. In this study, we investigated the effects of exogenous melatonin administration on the chronic hydrocephalus-induced hippocampal changes in infantile rats using histochemical and immunohistochemical techniques.…”

Novel Approaches of Oxidative Stress Mechanisms in the Multiple Sclerosis Pathophysiology and Therapy

“…Oxidative process may also be inhibited by NOS (41). It was reported that melatonin (10 mg daily/ 30 days) caused a statistically significant increase in antioxidative enzymes such as SOD and GPx and a decrease in malondialdehyde (MDA) in erythrocytes of SPMS patients (42).…”