title: Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells.
abstract: 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 tightly correlated with Wnt/β-catenin signaling pathway, and also to explore the mechanisms, which will provide a novel therapeutic intervention for treatment of Alzheimer's disease. Plasmid APPswe and BACE1-mychis were transiently co-transfected into SHSY5Y cells by Liposfectamin™2000. The cells were treated with Curcumin at 0, 1.25, 5.0, 20.0 μmol/L for 24 h, or with Curcumin at 5.0 μmol/L for 0, and 12, 24 and 48 h for time course assay. Cell lysates were collected for RT-PCR, Western blot assay and immunofluorescent staining were carried out for detecting the effect of Curcumin on the expression of GSK-3β, β-catenin and CyclinD1. RT-PCR and Western blot results showed that the expression of GSK-3β mRNA and protein significantly decreased in the transfected cells treated with Curcumin, and that the changes were in a dose and time-dependent manner (P<0.05); however, the protein expression of GSK-3β-Ser9 was increased (P<0.05). Meanwhile, the expressions of β-catenin and transcriptional factors CyclinD1 mRNA and protein increased and the changes were also in a dose and time-dependent manner (P<0.05). Immunofluorescent staining results not only confirmed the above changes, but also showed that β-catenin had translocated into the nucleus gradually with the increased dosage of Curcumin. Therefore, GSK-3β is a potential target for treatment of AD. Curcumin could activate the Wnt/β-catenin signaling pathway through inhibiting the expression of GSK-3β and inducing the expression of β-catenin and CyclinD1, which will provide a new theory for treatment of neurodegenerative diseases by Curcumin.
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.forename: Wen-ke
authors.initials: WK
authors.lastname: Yin
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Shi
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018613:Microscopy, Confocal; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; C530104:CCND1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D003474:Curcumin