Melatonin reduces oxidative catastrophe in neurons and glia

Melatonin, the chief secretory product of the pineal gland, is an uncommonly effective direct free radical scavenger and indirect antioxidant. It detoxifies both reactive oxygen (ROS) and reactive nitrogen species (RNS), both groups of which are abundantly produced in the brain. Endogenously-generated melatonin is discharged from pinealocytes into the rich capillary plexus in the gland and may also be released directly into the cerebrospinal fluid (CSF). In the few species where it has been investigated, CSF levels of melatonin greatly exceed its concentrations in the blood. From both the CSF and the blood melatonin readily enters the brain to protect neurons and glia from molecular damage induced by ROS/RNS. Melatonin's efficacy in reducing molecular damage resulting from toxic oxygen and nitrogen derivatives in both the brain and spinal cord supports the notion that this non-toxic molecule may have utility in forestalling and/or delaying the development and progression of neurodegenerative diseases that have a massive free radical component. The disease models of interest and in which melatonin has been most thoroughly tested include Alzheimer disease, Parkinson disease and to a lesser extent Huntington disease and amyotrophic lateral sclerosis. The experimental findings summarized herein clearly document that melatonin readily prevents oxidative damage to both neurons and glia. In doing so, it greatly reduces apoptosis of critical cells within the central nervous system.