Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation

Beta-amyloid (A beta) aggregation has been strongly associated with the neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's disease (AD). Inhibition of A beta assembly, destabilization of preformed A beta aggregates and attenuation of the cytotoxicity of A beta oligomers and fibrils could be valuable therapeutics of patients with AD. Recent studies suggested that moderate consumption of red wine and intake of dietary polyphenols, such as resveratrol, may benefit AD phenotypes in animal models and reduce the relative risk for AD clinical dementia. To understand the mechanism of this neuroprotection, we studied the effects of resveratrol, an active ingredient of polyphenols in wine and many plants, on the polymerization of A beta 42 monomer, the destabilization of A beta 42 fibril and the cell toxicity of A beta 42 in vitro using fluorescence spectroscopic analysis with thioflavin T (ThT), transmission electron microscope (TEM), circular dichroism (CD) and MTT assay. The results showed that resveratrol could dose-dependently inhibit A beta 42 fibril formation and cytotoxicity but could not prevent A beta 42 oligomerization. The studies by Western-blot, dot-blot and ELISA confirmed that the addition of resveratrol resulted in numerous A beta 42 oligomer formation. In conjunction with the concept that A beta oligomers are linked to A beta toxicity, we speculate that aside from potential antioxidant activities, resveratrol may directly bind to A beta 42, interfere in A beta 42 aggregation, change the A beta 42 oligomer conformation and attenuate A beta 42 oligomeric cytotoxicity. (C) 2009 Elsevier Inc. All rights reserved.