Melatonin defeats neurally-derived free radicals and reduces the associated neuromorphological and neurobehavioral damage

Russel J. Reiter, D. X. Tan, L. C. Manchester, H. Tamura

Research output: Contribution to journalReview articlepeer-review

90 Scopus citations


Melatonin and its metabolites are potent antioxidants by virtue of their ability to scavenge both oxygen-based and nitrogen-based radicals and intermediates but also as a consequence of their ability to stimulate the activity of antioxidative enzymes. Melatonin also prevents electron leakage from the mitochondrial electron transport chain thereby diminishing free radical generation; this process is referred to as radical avoidance. The fact that melatonin and its metabolites are all efficient radical scavengers indicates that melatonin is a precursor molecule for a variety of intracellular reducing agents. In specific reference to the brain, melatonin also has an advantage over some other antioxidants given that it readily passes through the blood-brain-barrier. This, coupled with the fact that it and its by-products are particularly efficient detoxifiers of reactive species, make these molecules of major importance in protecting the brain from oxidative/nitrosative abuse. This review summarizes the literature on two brain-related situations, i.e., traumatic brain and spinal cord injury and ischemia/reperfusion, and the neurodegenerative disease, amyotrophic lateral sclerosis, where melatonin has been shown to have efficacy in abating neural damage. These, however, are not the only age-associated neurodegenerative states where melatonin has been found to be protective.

Original languageEnglish (US)
Pages (from-to)5-22
Number of pages18
JournalJournal of Physiology and Pharmacology
Issue numberSUPPL. 6
StatePublished - Dec 2007


  • Amyotrophic lateral sclerosis
  • Antioxidant
  • Central nervous system
  • Free radical scavenger
  • Ischemia-reperfusion
  • Melatonin
  • Traumatic brain injury

ASJC Scopus subject areas

  • Physiology
  • Pharmacology


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