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- W2024477164 abstract "The activity of protein phosphatase 2A (PP2A) is decreased and promotes the hyperphosphorylation of tau in the brains of Alzheimer's Disease, but the mechanism for PP2A inactivation has not been elucidated. Previous studies had found that phosphorylation of PP2A catalytic subunit (PP2Ac) at the Tyrosine 307(Y307) site inactivated PP-2A potently. As an inducer of tyrosine phosphorylation, zinc has the possibility to phosphorylate PP2A. The effects of zinc on PP2A activity and tau phosphorylation were then investigated in this study. Rats were deeply anesthetized and divided into experimental group for brain injection with zinc sulfate, and control group for brain injection with PBS. The experimental group is further divided into two groups with or without treatment of zinc chelator clioquinol (CQ) after the zinc injection. One day or six days after the injection, the rats were sacrificed and the hippocampus was homogenated, the activity of PP2A, phosphorylation levels of tau and PP2A were detected by enzyme activity assay and western blotting. Src pathway was blocked by src SiRNA or inhibitor PP-2, then the effects of zinc on PP2A and tau were detected in N2a cells. Zinc treatment induced PP2A inhibition accompanied with PP2Ac (Y307) phosphorylation and tau hyperphosphorylation at several AD-tau hyperphosphorylation sites (Ser396,Ser404,Ser214,Thr205) both in rat brains and N2a cells. Intracellular zinc chelator rescue PP2A inactivation by brain zinc injection. The inactivation and Y307 phosphorylation of PP2A, hyperphosphorylation of tau induced by zinc were partly blocked by src SiRNA and PP-2, indicating that src is involved in PP2A inhibition and tau phosphorylation by zinc. We conclude that zinc induces protein phosphatase 2A inactivation and tau hyperphosphorylation through Src dependent pathway. Zinc chelating is an effective way to rescue PP2A activity in AD brains." @default.
- W2024477164 created "2016-06-24" @default.
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- W2024477164 date "2010-07-01" @default.
- W2024477164 modified "2023-10-17" @default.
- W2024477164 title "P1-335: Zinc induces protein phosphatase 2A inactivation and tau hyperphosphorylation through src-dependent pathway" @default.
- W2024477164 doi "https://doi.org/10.1016/j.jalz.2010.05.888" @default.
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