Curcumin Reduces Aβ Generation Of Neurons By PPARγ Activation And BACE1 Inhibition

Objective: This study aims to investigate the effects of Curcumin on Aβgeneration inhibition in vitro and explore its potential mechanisms involving BACE1 and PPARγ.Methods: Plasmids APPswe and BACE1-mychis were transiently co-transfected in SH-SY5Y cells by LipofectaminTM 2000, then treated with Curcumin at 0 (control Group), 1.25, 5.0, 20.0μmol/L for 24 hr, or with Curcumin at 5μmol/L for 0, 12, 24 and 48 hrs for the time course assay. RT-PCR were performed to measure the endogenous levels of BACE1 and PPARγmRNA. Western Blotting were used to detect the protein expression of BACE1 and PPARγ. The majorβ- secretase cleavage product Aβ40/42 was detected byβ-amyloid 1-40 or 42 Colorimetric ELISA assay. RT-PCR were performed to measure the endogenous levels of BACE1 and PPARγmRNA in the control group (DMSO+Curcumin) and inhibition group (GW9662+Curcumin) after pretreated with PPARγantagonist GW9662. Western Blotting were used to detect the protein expression of BACE1 and PPARγin the control group and inhibition group.Results: The results showed that the mRNA level and protein level of BACE1 were decreased obviously in a dose- and time-dependent manner after treated with Curcumin in the cell line (P <0.05). Conversely, the expression of PPARγincreased after treated with Curcumin in both mRNA and protein levels, also they were in a dose- and time-dependt 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). The expression of BACE1 increased in both mRNA and protein levels by GW9662 in contrast to control group after pretreated with GW9662 (P <0.05). The expression of PPARγwas decreased in both mRNA and protein levels by GW9662 in contrast to control group(P <0.05).Conclusion: Aβgeneration could be obviously inhibited by Curcumin in co-transfected SH-SY5Y cell lines and that the protective mechanism of Curcumin in AD involves activation of PPARγand decreased BACE1 at gene and protein levels.In addition, PPARγwas able to regulate the gene expression of BACE1 that affects the generation of Aβ.