title: Mechanism of neuroprotection of melatonin against beta-amyloid neurotoxicity.
abstract: The main component of senile plaques in Alzheimer's disease (AD), aggregated amyloid beta peptide (βA), 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 βA 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 βA 1-40 and the fragments βA 25-40 and βA 1-28. Melatonin had no effect on the process of fibrillation of βA and did not alter βA-induced calcium signalling in astrocytes, but did significantly reduce the rate of βA-induced reactive oxygen species production and also protected astrocytes against the mitochondrial depolarisation. Thus, scavenging of reactive oxygen species by melatonin appears to be the primary effect of melatonin in protecting neurones and astrocytes against βA toxicity.
authors.affiliation: Department of General Biophysics, University of Lodz, Banacha Street 12/16, Lodz 90-237, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Ionov
authors.forename: V
authors.initials: V
authors.lastname: Burchell
authors.forename: B
authors.initials: B
authors.lastname: Klajnert
authors.forename: M
authors.initials: M
authors.lastname: Bryszewska
authors.forename: A Y
authors.initials: AY
authors.lastname: Abramov
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D008550:Melatonin