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 beta-amyloid protein (AP). A beta is generated from the beta-amyloid precursor protein (APP) through the proteolysis of beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. A beta(42) isoform is more easily aggregate and more toxic to neurons than any other A beta 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 A beta(42). APP and BACE1. We found that Cur was the most active curcuminoid fraction in suppressing A beta(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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.