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Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease
Author(s) -
Matsubara Etsuro,
BryantThomas Tara,
Pacheco Quinto Javier,
Henry Tracey L.,
Poeggeler Burkhard,
Herbert Donald,
CruzSanchez Felix,
Chyan YauJan,
Smith Mark A.,
Perry George,
Shoji Mikio,
Abe Koji,
Leone Anna,
GrundkeIkbal Inge,
Wilson Glen L.,
Ghiso Jorge,
Williams Christina,
Refolo Lorenzo M.,
Pappolla Miguel A.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01654.x
Subject(s) - melatonin , genetically modified mouse , transgene , amyloid (mycology) , medicine , endocrinology , oxidative phosphorylation , oxidative stress , pathogenesis , alzheimer's disease , biology , disease , pathology , biochemistry , gene
Increased levels of a 40–42 amino‐acid peptide called the amyloid β protein (Aβ) 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 Aβ‐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 Aβ, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time‐dependent elevation of β‐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.