The inhibitory effects of different curcuminoids on β-amyloid protein, β-amyloid precursor protein and β-site amyloid precursor protein cleaving enzyme 1 in swAPP HEK293 cells.
The hallmark of Alzheimer's disease (AD) is the accumulation of β-amyloid protein (Aβ). Aβ is generated from the β-amyloid precursor protein (APP) through the proteolysis of β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. Aβ(42) isoform is more easily aggregate and more toxic to neurons than any other Aβ isoforms, thus being regarded as the primary toxic specie in AD. Curcumin mix has potent anti-amyloidogenic effect and shows great promise for AD treatment and prevention. The present study was conducted to examine the effects of curcumin mix and its different curcuminoids including curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) on Aβ(42), APP and BACE1. We found that Cur was the most active curcuminoid fraction in suppressing Aβ(42) production and the order of inhibitory potency of other curcuminoids was DMC>curcumin mix>BDMC. Cur, but not other curcuminoids, could reduce APP protein expression and none of curcuminoids affected APP mRNA level. BDMC could reduce BACE1 mRNA and protein levels, while DMC only affected BACE1 mRNA expression. Our data indicate that the anti-amyloidogenic effect of Cur may be mediated through the modulation of APP, while the anti-amyloidogenic effect of BDMC may be mediated through the modulation of BACE1.
Liu
Hongying
H
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Li
Zhong
Z
Qiu
Donghai
D
Gu
Qiong
Q
Lei
Qingfeng
Q
Mao
Li
L
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D036381:Diarylheptanoids; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D036381:Diarylheptanoids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C034786:bisdemethoxycurcumin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D003474:Curcumin; C050229:demethoxycurcumin