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 Complexes 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.