Inhibition of Alzheimer β-fibrillogenesis by melatonin

Miguel Pappolla, Peter Bozner, Claudio Soto, Haiyan Shao, Nickolaos K. Robakis, Michael Zagorski, Blas Frangione, Jorge Ghiso

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285 Scopus citations

Abstract

It is generally postulated that the amyloid β protein (Aβ) plays a central role in the progressive neurodegeneration observed in Alsheimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of Aβ to form β-sheet structures or amyloid fibrils. We report that melatonin a hormone recently found to protect neurons against Aβ toxicity, interacts with Aβ1-40 and Aβ1-42 and inhibits the progressive formation of β-sheets and amyloid fibrils. These interactions between melatonin and the amyloid peptides were demonstrated by circular dichroism and electron microscopy for Aβ1-40 and Aβ-42 and by nuclear magnetic resonance spectroscopy for Aβ1-40. Inhibition of β-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.

Original languageEnglish (US)
Pages (from-to)7185-7188
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
StatePublished - Mar 27 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Pappolla, M., Bozner, P., Soto, C., Shao, H., Robakis, N. K., Zagorski, M., Frangione, B., & Ghiso, J. (1998). Inhibition of Alzheimer β-fibrillogenesis by melatonin. Journal of Biological Chemistry, 273(13), 7185-7188. https://doi.org/10.1074/jbc.273.13.7185