title: Inhibition of Alzheimer beta-fibrillogenesis by melatonin.
abstract: It is generally postulated that the amyloid beta protein (Abeta) plays a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of Abeta to form beta-sheet structures or amyloid fibrils. We report that melatonin, a hormone recently found to protect neurons against Abeta toxicity, interacts with Abeta1-40 and Abeta1-42 and inhibits the progressive formation of beta-sheets and amyloid fibrils. These interactions between melatonin and the amyloid peptides were demonstrated by circular dichroism and electron microscopy for Abeta1-40 and Abeta1-42 and by nuclear magnetic resonance spectroscopy for Abeta1-40. Inhibition of beta-sheets and fibrils could not be accomplished in control experiments when a free radical scavenger or a melatonin analog were substituted for melatonin under otherwise identical conditions. In sharp contrast with conventional anti-oxidants and available anti-amyloidogenic compounds, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential new therapeutic agent in Alzheimer's disease.
authors.affiliation: University of South Alabama College of Medicine, Mobile, Alabama 36617, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pappolla
authors.forename: P
authors.initials: P
authors.lastname: Bozner
authors.forename: C
authors.initials: C
authors.lastname: Soto
authors.forename: H
authors.initials: H
authors.lastname: Shao
authors.forename: N K
authors.initials: NK
authors.lastname: Robakis
authors.forename: M
authors.initials: M
authors.lastname: Zagorski
authors.forename: B
authors.initials: B
authors.lastname: Frangione
authors.forename: J
authors.initials: J
authors.lastname: Ghiso
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000494:pharmacology*; D008854:Microscopy, Electron; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000473:pathology; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D008550:Melatonin