MELATONIN PREVENTS DEATH OF NEUROBLASTOMA-CELLS EXPOSED TO THE ALZHEIMER AMYLOID PEPTIDE

Studies from several laboratories have generated evidence suggesting t hat oxidative stress is involved in the pathogenesis of Alzheimer's di sease (AD). The finding that the amyloid beta protein (A beta) has neu rotoxic properties and that such effects are, in part, mediated by fre e radicals has provided insights into mechanisms of cell death in AD a nd an avenue to explore new therapeutic approaches. In this study we d emonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracel lular Ca2+ increases induced by a cytotoxic fragment of A beta. The ef fects of melatonin were extremely reproducible and corroborated by mul tiple quantitative methods, including cell viability studies by confoc al laser microscopy, electron microscopy, and measurements of intracel lular calcium levels. The importance of this finding is that, in contr ast to conventional antioxidants, melatonin has a proposed physiologic al role in the aging process. Secretion levels of this hormone are dec reased in aging and more severely reduced in AD. The reported phenomen on may be of therapeutic relevance in AD.