title: Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease.
abstract: Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.
authors.affiliation: Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.forename: Tara
authors.initials: T
authors.lastname: Bryant-Thomas
authors.forename: Javier
authors.initials: J
authors.lastname: Pacheco Quinto
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Henry
authors.forename: Burkhard
authors.initials: B
authors.lastname: Poeggeler
authors.forename: Donald
authors.initials: D
authors.lastname: Herbert
authors.forename: Felix
authors.initials: F
authors.lastname: Cruz-Sanchez
authors.forename: Yau-Jan
authors.initials: YJ
authors.lastname: Chyan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Anna
authors.initials: A
authors.lastname: Leone
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Ikbal
authors.forename: Glen L
authors.initials: GL
authors.lastname: Wilson
authors.forename: Jorge
authors.initials: J
authors.lastname: Ghiso
authors.forename: Christina
authors.initials: C
authors.lastname: Williams
authors.forename: Lorenzo M
authors.initials: LM
authors.lastname: Refolo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pappolla
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Chain
authors.forename: Eyal
authors.initials: E
authors.lastname: Neria
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009566:Nitrates / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D015996:Survival Rate
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009566:Nitrates; D011506:Proteins; D008550:Melatonin