Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity.
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.
Feng
Ying
Y
Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001, China.
Yang
Shi-gao
SG
Du
Xue-ting
XT
Zhang
Xi
X
Sun
Xiao-xia
XX
Zhao
Min
M
Sun
Gui-yuan
GY
Liu
Rui-tian
RT
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
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D004610:Ellagic Acid