Curcumin Activites Wnt/β-Catenin Signaling Pathway Through Inhibiting The Activity Of GSK-3β To Prevent Alzheimer's Disease In Vitro

Objective:Wnt/β-catenin signaling pathway plays an important role in the genesis and development of Alzheimer's disease.The study aims to investigate the effect of Curcumin on the expression of GSK-3β,β-catenin and CyclinD1 in vitro,which are correlated tightly with Wnt/β-catenin signaling pathway,and the effect of the generation of Aβ, and to explore their mechanisms,which will provide a novel therapeutic intervention for treating with Alzheimer's disease.Methods:Plasmid APPswe and BACE1-mychis were transiently co-transfected in SHSY5Y cells by Liposfectamin^TM2000.The cells were treated with Curcumin at at 0,1.25,5.0,20.0μmol/L for 24 h,or with Curcumin at 5.0μmol/L for 0,12,24 and 48 h for the time course assay.Then collecting media was for RT-PCR,Westen blot,and cell slides for immuno-fluoresecnt staining,to detect the effect of Curcumin on the expression of GSK-3β,β-catenin.The generation of Aβ42 and Aβ40 was detected by ELISA. Results:RT-PCR and Western blot results showed that in the transfected cells after treatment with Curcumin,the expression of GSK-3βmRNA and protein significantly decreased,and the changes were in a dose-and time-dependent manner(p＜0.05),but the protein expression of GSK-3β-Ser9 increased(p＜0.05).Meanwhile,the expression ofβ-catenin and transcriptional factors CyclinD1 mRNA and protein increased,and the changes also were in a dose-and time-dependent manner(p＜0.05),too.Immuno-fluoresecnt staining results not only confirmed the above changes,but also suggested thatβ-catenin had translocated into the nuclear gradually with the increased dosage of Curcumin.ELISA results showed that the generation of AJ340/42 reduced significantly,and also was in a dose-and time-dependent manner(p＜0.05).Conclusion:GSK-3βis a potential target for treating with AD.The mechanism of Curcumin playing its important role of preventing from AD is that it can activate the Wnt/β-catenin signaling pathway through inhibiting the expression of GSK-3βand inducing the expression ofβ-catenin and CyclinD1.The results will provide a new pathway of Curcumin for treating with neurodegenerative disease.