Morroniside-Induced PP2A Activation Antagonizes Tau Hyperphosphorylation in a Cellular Model of Neurodegeneration

Journal of Alzheimer's Disease : JAD
Cui-Cui YangLan Zhang

Abstract

An accumulation of hyperphosphorylated tau in the brain is a hallmark of Alzheimer's disease (AD). Deficits in protein phosphatase 2A (PP2A) are associated with tau hyperphosphorylation in AD. To investigate the effects of morroniside (MOR), isolated from Cornus officinalis, on tau hyperphosphorylation and its underlying mechanisms related to PP2A. SK-N-SH cells were pretreated with 50-200 μM MOR for 24 h followed by 20 nM okadaic acid (OA) for 6 h. PP2Ac siRNA was transfected into HEK293 cells to determine the direct interaction of MOR with PP2A. Western blotting was used to measure the expression of proteins and enzymes. PP2A activity was measured by molybdenum blue spectrophotometry. Pretreatment with MOR improved the cellular morphological damage and inhibited tau hyperphosphorylation in SK-N-SH cells induced by OA, a PP2A inhibitor. Moreover, MOR increased PP2A activity, concurrent with a decrease in the expression of demethylated PP2A at Leu309 and phosphorylated PP2A at Tyr307. MOR decreased protein phosphatase methylesterase 1 (PME-1) expression and the ratio of PME-1/leucine carboxyl methyltransferase 1 (LCMT-1). Furthermore, MOR treatment decreased the phosphorylation of Src at Tyr416, which regulates the phosphorylat...Continue Reading

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Citations

May 24, 2016·International Journal of Molecular Sciences·Chao FangJianmin Li
Sep 14, 2018·Frontiers in Pharmacology·Monika E Czerwińska, Matthias F Melzig
Dec 31, 2019·Cellular and Molecular Life Sciences : CMLS·Jiyeon Seo, Mikyoung Park
Jun 11, 2020·The Journal of Physiological Sciences : JPS·Huiming ZhangLibo Zou
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May 16, 2017·Journal of Medicinal Chemistry·Zakey Yusuf BuuhRongsheng E Wang

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