title: Curcumin attenuates amyloid-β-induced tau hyperphosphorylation in human neuroblastoma SH-SY5Y cells involving PTEN/Akt/GSK-3β signaling pathway.
abstract: Accumulated amyloid-β peptide (Aβ) and hyperphosphorylated tau proteins are two hallmarks of Alzheimer's disease (AD). Increasing evidence suggests that Aβ induces tau hyperphosphorylation in AD pathology, but the signaling pathway is not completely understood. Inhibiting Aβ-induced cellular signaling is beneficent to AD treatment. In this study, cellular signaling of tau phosphorylation induced by Aβ and the inhibiting effects of curcumin on this signaling were investigated on human neuroblastoma SH-SY5Y cells. The results indicated that curcumin inhibits Aβ-induced tau phosphorylation at Thr231 and Ser396, over-expression of HDAC6, and decrease in phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9. However, the protective effect of curcumin on dephosphorylation of GSK-3β induced by Aβ is not directly related to cellular oxidative stress. Curcumin depresses Aβ-induced down-regulation of phosphorylations of Akt at Thr308 and Ser473 and 3-phosphoinositide-dependent protein kinase 1 at Ser241, implying that second message PIP3 involves curcumin-protective cell signaling. Furthermore, insulin receptor/phosphatidyl inositol 3-kinase pathway, as a regulatory signaling of second message PIP3, does not participate in Aβ-induced deactivation of Akt (dephosphorylation at Thr308 and Ser473). However, Aβ results in over-expression of Phosphatase and tensin homolog (PTEN), a negative regulator of PIP3. Curcumin depresses Aβ-induced up-regulation of PTEN induced by Aβ. These results imply that curcumin inhibits Aβ-induced tau hyperphosphorylation involving PTEN/Akt/GSK-3β pathway.
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University , Beijing , People's Republic of China .
authors.forename: Han-Chang
authors.initials: HC
authors.lastname: Huang
authors.forename: Di
authors.initials: D
authors.lastname: Tang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Jiang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D003474:Curcumin