Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease

Etsuro Matsubara, Tara Bryant-Thomas, Javier Pacheco Quinto, Tracey L. Henry, Burkhard Poeggeler, Donald Herbert, Felix Cruz-Sanchez, Yau Jan Chyan, Mark A. Smith, George Perry, Mikio Shoji, Koji Abe, Anna Leone, Inge Grundke-Ikbal, Glen L. Wilson, Jorge Ghiso, Christina Williams, Lorenzo M. Refolo, Miguel A. Pappolla

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1101-1108
Number of pages8
JournalJournal of Neurochemistry
Volume85
Issue number5
DOIs
Publication statusPublished - Jun 2003

Keywords

  • Alzheimer
  • Dementia
  • Melatonin
  • Oxidative stress
  • Protein nitration
  • β-amyloid

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Matsubara, E., Bryant-Thomas, T., Quinto, J. P., Henry, T. L., Poeggeler, B., Herbert, D., Cruz-Sanchez, F., Chyan, Y. J., Smith, M. A., Perry, G., Shoji, M., Abe, K., Leone, A., Grundke-Ikbal, I., Wilson, G. L., Ghiso, J., Williams, C., Refolo, L. M., & Pappolla, M. A. (2003). Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. Journal of Neurochemistry, 85(5), 1101-1108. https://doi.org/10.1046/j.1471-4159.2003.01654.x