title: Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity.
abstract: Smaller, soluble oligomers of beta-amyloid (Abeta) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of Abeta oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against Abeta neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on Abeta42 aggregation and neurotoxicity in vitro. EA promoted Abeta fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited Abeta aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in Abeta42 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 Abeta aggregates to render them harmless, our MTT results showed that EA could significantly reduce Abeta42-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.
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Shi-gao
authors.initials: SG
authors.lastname: Yang
authors.forename: Xue-ting
authors.initials: XT
authors.lastname: Du
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Gui-yuan
authors.initials: GY
authors.lastname: Sun
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D004610:Ellagic Acid / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D004610:Ellagic Acid