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

Beta-amyloid (Aβ) aggregation has been strongly associated with the neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's disease (AD). Inhibition of Aβ assembly, destabilization of preformed Aβ aggregates and attenuation of the cytotoxicity of Aβ 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 Aβ42 monomer, the destabilization of Aβ42 fibril and the cell toxicity of Aβ42 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 Aβ42 fibril formation and cytotoxicity but could not prevent Aβ42 oligomerization. The studies by Western-blot, dot-blot and ELISA confirmed that the addition of resveratrol resulted in numerous Aβ42 oligomer formation. In conjunction with the concept that Aβ oligomers are linked to Aβ toxicity, we speculate that aside from potential antioxidant activities, resveratrol may directly bind to Aβ42, interfere in Aβ42 aggregation, change the Aβ42 oligomer conformation and attenuate Aβ42 oligomeric cytotoxicity.