Journal
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
Volume 34, Issue 1, Pages 26-37Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10799893.2013.848891
Keywords
Amyloid-beta; Alzheimer's disease; curcumin; GSK-3 beta; PTEN; tau hyperphosphorylation
Categories
Funding
- National Natural Science Foundation of China [31071512]
- Scientific Research Common Program of Beijing Municipal Commission of Education [SQKM201411417003]
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Accumulated amyloid-beta peptide (A beta) and hyperphosphorylated tau proteins are two hallmarks of Alzheimer's disease (AD). Increasing evidence suggests that A beta induces tau hyperphosphorylation in AD pathology, but the signaling pathway is not completely understood. Inhibiting A beta-induced cellular signaling is beneficent to AD treatment. In this study, cellular signaling of tau phosphorylation induced by A beta and the inhibiting effects of curcumin on this signaling were investigated on human neuroblastoma SH-SY5Y cells. The results indicated that curcumin inhibits A beta-induced tau phosphorylation at Thr231 and Ser396, over-expression of HDAC6, and decrease in phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) at Ser9. However, the protective effect of curcumin on dephosphorylation of GSK-3 beta induced by A beta is not directly related to cellular oxidative stress. Curcumin depresses A beta-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 A beta-induced deactivation of Akt (dephosphorylation at Thr308 and Ser473). However, A beta results in over-expression of Phosphatase and tensin homolog (PTEN), a negative regulator of PIP3. Curcumin depresses A beta-induced up-regulation of PTEN induced by A beta. These results imply that curcumin inhibits A beta-induced tau hyperphosphorylation involving PTEN/Akt/GSK-3 beta pathway.
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