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 Pappolla

Research output: Contribution to journalArticle

232 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 (US)
Pages (from-to)1101-1108
Number of pages8
JournalJournal of Neurochemistry
Volume85
Issue number5
DOIs
StatePublished - Jun 2003
Externally publishedYes

Fingerprint

Pathology
Melatonin
Amyloid
Alzheimer Disease
Survival
Nitration
Transgenic Mice
Serum Amyloid A Protein
Amyloidosis
Brain
Proteins
Aging of materials
Hormones
Amino Acids
Peptides

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. / Matsubara, Etsuro; Bryant-Thomas, Tara; Quinto, Javier Pacheco; Henry, Tracey L.; Poeggeler, Burkhard; Herbert, Donald; Cruz-Sanchez, Felix; Chyan, Yau Jan; Smith, Mark A.; Perry, George; Shoji, Mikio; Abe, Koji; Leone, Anna; Grundke-Ikbal, Inge; Wilson, Glen L.; Ghiso, Jorge; Williams, Christina; Refolo, Lorenzo M.; Pappolla, Miguel.

In: Journal of Neurochemistry, Vol. 85, No. 5, 06.2003, p. 1101-1108.

Research output: Contribution to journalArticle

Matsubara, E, Bryant-Thomas, T, Quinto, JP, Henry, TL, Poeggeler, B, Herbert, D, Cruz-Sanchez, F, Chyan, YJ, Smith, MA, Perry, G, Shoji, M, Abe, K, Leone, A, Grundke-Ikbal, I, Wilson, GL, Ghiso, J, Williams, C, Refolo, LM & Pappolla, M 2003, 'Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease', Journal of Neurochemistry, vol. 85, no. 5, pp. 1101-1108. https://doi.org/10.1046/j.1471-4159.2003.01654.x
Matsubara, Etsuro ; Bryant-Thomas, Tara ; Quinto, Javier Pacheco ; Henry, Tracey L. ; Poeggeler, Burkhard ; Herbert, Donald ; Cruz-Sanchez, Felix ; Chyan, Yau Jan ; Smith, Mark A. ; Perry, George ; Shoji, Mikio ; Abe, Koji ; Leone, Anna ; Grundke-Ikbal, Inge ; Wilson, Glen L. ; Ghiso, Jorge ; Williams, Christina ; Refolo, Lorenzo M. ; Pappolla, Miguel. / Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. In: Journal of Neurochemistry. 2003 ; Vol. 85, No. 5. pp. 1101-1108.
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