INHIBITION OF ALZHEIMER BETA-FIBRILLOGENESIS BY MELATONIN

It is generally postulated that the amyloid beta protein (A beta) play s a central role in the progressive neurodegeneration observed in Alzh eimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of A beta to form beta-sheet structures or amyloid fibril s. We report that melatonin, a hormone recently found to protect neuro ns against A beta toxicity, interacts with A beta 1-40 and A beta 1-42 and inhibits the progressive formation of beta-sheets and amyloid fib rils. These interactions between melatonin and the amyloid peptides we re demonstrated by circular dichroism and electron microscopy for A be ta 1-40 and A beta 1-42 and by nuclear magnetic resonance spectroscopy for A beta 1-40. Inhibition of beta-sheets and fibrils could not be a ccomplished in control experiments when a free radical scavenger or a melatonin analog were substituted for melatonin under otherwise identi cal conditions. In sharp contrast with conventional anti-oxidants and available anti-amyloidogenic compounds, melatonin crosses the blood-br ain barrier, is relatively devoid of toxicity, and constitutes a poten tial new therapeutic agent in Alzheimer's disease.