Role of melatonin in neurodegenerative diseases

Abstract

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. 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, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury.

Melatonin Metabolism in the Central Nervous System

“…In this context, it may be briefly noted that the brain AAAs have recently, and somehow unexpectedly, re-gained some interest after they were shown to be inhibited by several investigational anti-Alzheimer drugs considered for human treatment [20,22,100]. With regard to the attempts of antagonizing Alzheimer's disease by melatonin [85,95,130,131], this possibility may be kept in mind, although melatonin exhibits numerous other properties of interest in this neurodegenerative disorder.…”

“…This metabolite and also its secondary product, N 1 -acetyl-5-methoxykynuramine (AMK), have been shown to possess cell-protective properties including beneficial effects in mitochondria [1,40,41,50,71,136,143]. Moreover, numerous publications have demonstrated the neuroprotective potential of melatonin under various experimental conditions [11,85,104,105,108,118,131,154]. For this purpose, elevated doses of melatonin strongly exceeding physiological levels have to be used, especially under acute conditions requiring the prevention of neuronal dysfunction.…”

Grape Secondary Metabolites – Benefits for Human Health

“…The protective effect is suggested to be complex due to the multiple targets involved in the melatonin action against oxidative stress, which is reviewed by Srinivasan (2002) and Srinivasan et al (2005). However, some studies, summarized in the profound review of Srinivasan et al (2006), reported about adverse effect of melatonin leading to aggravation of motor deficit in animal models of PD.…”

Antioxidant potential of melatonin enhances the response to L-dopa in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice

“…Studies have demonstrated that melatonin has antioxidant properties by acting as a free radical scavenger [52]. Melatonin has been also associated with the cellular antioxidant defense.…”