MECHANISM OF NEUROPROTECTION OF MELATONIN AGAINST BETA-AMYLOID NEUROTOXICITY

The main component of senile plaques in Alzheimer's disease (AD), aggregated amyloid beta peptide (beta A), is neurotoxic and implicated in AD pathology. Melatonin is a hormone secreted from the pineal gland, levels of which are decreased in aging, particularly in AD subjects. This hormone is known to possess neuroprotective properties against beta A toxicity in vivo, but the mechanism of protection remains controversial. In cultures of mixed neurones and astrocytes, we find that melatonin is protective against neuronal and astrocytic death induced by aggregated full length beta A 1-40 and the fragments beta A 25-40 and beta A 1-28. Melatonin had no effect on the process of fibrillation of beta A and did not alter beta A-induced calcium signalling in astrocytes, but did significantly reduce the rate of beta A-induced reactive oxygen species production and also protected astrocytes against the mitochondria! depolarisation. Thus, scavenging of reactive oxygen species by melatonin appears to be the primary effect of melatonin in protecting neurones and astrocytes against beta A toxicity. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.