Estudios científicos
Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation
Abstract:
Beta-amyloid (Abeta) aggregation has been strongly associated with the neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's disease (AD). Inhibition of Abeta assembly, destabilization of preformed Abeta aggregates and attenuation of the cytotoxicity of Abeta 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 Abeta42 monomer, the destabilization of Abeta42 fibril and the cell toxicity of Abeta42 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 Abeta42 fibril formation and cytotoxicity but could not prevent Abeta42 oligomerization. The studies by Western-blot, dot-blot and ELISA confirmed that the addition of resveratrol resulted in numerous Abeta42 oligomer formation. In conjunction with the concept that Abeta oligomers are linked to Abeta toxicity, we speculate that aside from potential antioxidant activities, resveratrol may directly bind to Abeta42, interfere in Abeta42 aggregation, change the Abeta42 oligomer conformation and attenuate Abeta42 oligomeric cytotoxicity.
Comentarios divulgativos:
La aglutinación de beta-amiloides (Abeta) se ha asociado con la neurodegeneración patológica y la enfermedad de alzheimer. La inhibición del ensamblamiento de abeta y desastabilización de los agrgados de Abeta puede ser un modelo para evaluar a los pacientes con alzheimer. Estudios recientes sugieren que la consumición de vino tinto y de polifenoles como el resveratrol puede beneficiar los diferentes fenotipos del Alzheimer y reducir los riesgos de demencia en esta enfermedad. Para entender el mecanismo de esta neuroprotección se estudian los efectos del resveratrol en la polimeriozación del monomero Abeta42, la desestabilización de Abeta42 y la toxicidad de este in vitro.
