Ellagic acid promotes Aβ42 fibrillization and inhibits Aβ42-induced neurotoxicity

Smaller, soluble oligomers of beta-amyloid (A beta) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A beta oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A beta neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A beta 42 aggregation and neurotoxicity in vitro. EA promoted A beta fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A beta aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A beta 42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A beta aggregates to render them harmless, our MTT results showed that EA could significantly reduce A beta 42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD. (C) 2009 Elsevier Inc. All rights reserved.