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J Biol Chem, Vol. 273, Issue 13, 7185-7188, March 27, 1998

COMMUNICATION
Inhibition of Alzheimer -Fibrillogenesis by Melatonin

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

From the  University of South Alabama College of Medicine, Mobile, Alabama 36617, ^§ New York University, New York, New York 10016, ^¶ Case Western Reserve University, Cleveland, Ohio 44106, and  Mount Sinai Medical School, New York, New York 10029

It is generally postulated that the amyloid  protein (A) plays a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of A to form -sheet structures or amyloid fibrils. We report that melatonin, a hormone recently found to protect neurons against A toxicity, interacts with A1-40 and A1-42 and inhibits the progressive formation of -sheets and amyloid fibrils. These interactions between melatonin and the amyloid peptides were demonstrated by circular dichroism and electron microscopy for A1-40 and A1-42 and by nuclear magnetic resonance spectroscopy for A1-40. Inhibition of -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.

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