Cornel Iridoid Glycoside Inhibits Tau Hyperphosphorylation via Regulating Cross-Talk Between GSK-3β and PP2A Signaling

Frontiers in Pharmacology
Cuicui YangLan Zhang

Abstract

Neurofibrillary pathology contributes to neuronal dysfunction and correlates with the clinical progression of Alzheimer's disease (AD). Tau phosphorylation is mainly regulated by a balance of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) activities. Cornel iridoid glycoside (CIG) is a main component extracted from Cornus officinalis. The purpose of this study was to investigate the effects of CIG on GSK-3β and PP2A, thus to explore the mechanisms of CIG to inhibit tau hyperphosphorylation. The rat model of tau hyperphosphorylation was established by intraventricular injection of wortmannin and GF-109203X (GFX) to activate GSK-3β. The results showed that intragastrical administration of CIG inhibited tau hyperphosphorylation in the brain of rats induced by wortmannin/GFX. The results in vivo and in vitro exhibited that CIG inhibited tau hyperphosphorylation and GSK-3β over-activation. In the mechanism of action, CIG's attenuating GSK-3β activity was found to be dependent on PI3K/AKT signaling pathway. PP2A catalytic C subunit (PP2Ac) siRNA abrogated the effect of CIG on PI3K/AKT/GSK-3β. Additionally and crucially, we also found that CIG inhibited the demethylation of PP2Ac at Leu309 in vivo and in vitro....Continue Reading

References

Sep 1, 1993·Journal of Neurochemistry·C X GongK Iqbal
Jan 1, 1997·Journal of Neuropathology and Experimental Neurology·J J PeiI Grundke-Iqbal
Mar 22, 2001·Experimental Neurology·V Vogelsberg-RagagliaV M Lee
Aug 25, 2001·Annual Review of Neuroscience·V M LeeJ Q Trojanowski
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Apr 22, 2004·Journal of Neuropathology and Experimental Neurology·Estelle SontagCharles L White
Nov 13, 2004·Journal of Neuropathology and Experimental Neurology·Estelle SontagCharles L White
Nov 3, 2005·The European Journal of Neuroscience·Fei LiuCheng-Xin Gong
Feb 9, 2006·Neurobiology of Aging·Patrizia De SarnoRichard S Jope
Feb 14, 2006·Current Alzheimer Research·John Hardy
Sep 1, 2006·Neurochemical Research·Richard S JopeEléonore Beurel
Jul 1, 2008·Biochimica Et Biophysica Acta·Pieter J A EichhornRené Bernards
Feb 28, 2009·Trends in Molecular Medicine·Diane P HangerWendy Noble
Mar 24, 2010·Journal of Alzheimer's Disease : JAD·Wei QianFei Liu
Feb 5, 2011·Molecular Cell·Vitali StanevichYongna Xing
Apr 8, 2011·Science Translational Medicine·David M HoltzmanAlison M Goate
Jun 8, 2011·Future Medicinal Chemistry·Michael VoronkovJeffry B Stock
Feb 16, 2012·The Journal of Biological Chemistry·Xu-Ying SunJian-Zhi Wang
Apr 27, 2012·Frontiers in Molecular Neuroscience·Akihiko Takashima
Jun 13, 2012·International Journal of Alzheimer's Disease·Michala KolarovaDaniela Ripova
Sep 21, 2013·Acta Neuropathologica·Patrick L McGeer, Edith G McGeer
Jan 24, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Cui-Cui YangLan Zhang
Jul 18, 2014·Alzheimer's Research & Therapy·Yasuko KitagishiSatoru Matsuda
Jul 3, 2015·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Satoshi IkemaMasaharu Komatsu
Jul 5, 2015·Molecular Neurobiology·Eduardo R ZimmerLuis V Portela

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Citations

Jun 30, 2019·Journal of Cellular Physiology·Huaiqing LuoJin Xu
Nov 4, 2020·European Journal of Medicinal Chemistry·Lisha WangBengt Winblad
Dec 18, 2020·Frontiers in Molecular Neuroscience·Zhang MaoWang Wen-Ya
May 10, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Prajakta A DhageShidin Balakrishnan
Sep 24, 2020·Behavioural Neurology·Tingting PiJingshan Shi

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Methods Mentioned

BETA
transfection
protein assay
electrophoresis
transgenic

Software Mentioned

SPSS
TINA

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