The Regulation Of Curcumin On The Amyloidogentic Pathaway Of APP In Alzheimer's Disease

Objective: It was reported that as a promising prevention and therapeutic intervention in Alzheimer's disease, Curcumin could obviously inhibit the generation of Aβ, but the mechanism is not fully defined.APP undergoesβ-andγ-secretase cleavages to generate Aβin the amyloidogenic pathway. This study aims to investigate the effects of Curcumin on the APP processing in the amyloidogenic pathway in vitro and explore its mechanisms on Aβgeneration inhibition.Methods: Plasmids APPswe and BACE1-mychis were transiently co-transfected in SH-SY5Y and HEK293 cells by LipofectaminTM2000.The two cell lines then treated with Curcumin at 0, 1.25, 5, 20μmol/L for 24 h, or with Curcumin at 5μmol/L for 0, 12, 24 and 48 h for the time course assay. RT-PCR were performed to measure the endogenous levels of APP and BACE1 mRNA. Western Blotting were used to detect the protein expression of BACE1 and C99, the majorβ- secretase cleavage product. The concentration of Aβ40/42 was detected byβ-amyloid 1-40 or 42 Colorimetric ELISA. Results: RT-PCR results showed that the mRNA levels of APP and BACE1 were decreased obviously in a dose- and time-dependent manner after treated with Curcumin in the two cell lines (p<0.05). Furthermore, this change was more significant in transfected SH-SY5Y cells. Western Blotting results showed that the expression of BACE1 and C99 protein were all decreased in a dose- and time-dependent manner (p<0.05). ELISA results showed that the generation of Aβ40/42 reduced significantly, also in a dose- and time-dependent manner (p<0.05).Conclusion: Our finding demonstrated that Curcumin could inhibit the expression of the APP at mRNA; the expression of the BACE1 at mRNA and protein levels, furthermore it could inhibit the generation of Aβ40/42, and those changes were dose-time dependent (p<0.05).Those factors are key components in APP amyloidogenic pathway.Our study indicates that Aβ40/42 generation inhibition effect of Curcumin might due to its influence on amyloidogenic pathway.This may provide important experimental basis for AD treatment with Curcumin.