The Resveratrol Derivative Piceatannol Alters the Conformation of Alzheimer's Disease Associated Aβ Protein Aggregates

Abstract

Epidemiological evidence suggests that moderate red wine intake is associated with a reduction of risk in Alzheimer's disease (AD). Together with the fact that natural polyphenol resveratrol is highly abundant in red wine, it is speculated that resveratrol and its derivatives may play a role in preventing the progression of AD. This study investigated the behavior of resveratrol and its derivatives, piceatannol, oxyresveratrol and piceid in interacting with AD associated protein Aβ peptides whose aggregation is hypothesized to contribute to the pathogenesis of AD.The inhibitory capability of resveratrol and derivatives toward Aβ monomer aggregation was evaluated using dot blotting with LOC antibody, which binds to amyloid aggregate fibril structure. Piceatannol exhibited a significant 90% decrease of LOC recognized amyloid aggregate β structure. In contrast, other compounds elicited only a modest effect. TEM images reveal that this decrease is a result of changes in fibril structure. Moreover, piceatannol is able to induce morphology changes in pre-formed Aβ aggregates. When inhibition of the early stages of aggregation was examined using an oligomerization assay that employs SDS-PAGE and Western blot to determine the quantity and size of oligomers formed. None of the compounds are effective inhibitors at this stage of aggregation. Thus, the morphology changes induced by piceatannol occur post oligomerization.Finally, to assess the impact of Aβ aggregates’ morphology on neurotoxicity, a neuronal apoptosis assay was used to assess the toxicity of morphology-altered aggregates. Together, results suggests piceatannol to be a potential therapeutic agent for AD.