Cross talk between PI3K-AKT-GSK-3β and PP2A pathways determines tau hyperphosphorylation

Wang, Yixuan; Yang, Riyun; Gu, Jianlan; Yin, Xiaomin; Jin, Nana; Xie, Shutao; Wang, Yifan; Chang, He; Qian, Wei; Shi, Jing; Iqbal, Khalid; Chen, Gong; Cheng, Chun; Liu, Fei

doi:10.1016/j.neurobiolaging.2014.07.035

Cited by 109 publications

(79 citation statements)

References 56 publications

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“…Single cell gene expression studies showed an upregulation of ChAT expression as well as stable levels of mRNAs encoding select subclasses of protein phosphatase subunits (PP1a and PP1g) in GAL hyperinnervated CBF neurons but downregulation in those not hyperinnervated by GAL in AD (Counts et al, 2008; 2009; 2010). Reduced activity of PP1 and PP2A subunits is implicated in tau hyperphosphorylation, which in turn precipitates NFT pathology and subsequent cytoskeletal destabilization in vulnerable neurons (Mawal-Dewan et al, 2004: Yoshiyama et al, 2013; Wang et al, 2015). Taken together, these observations suggest that GAL remodeling may delay NFT pathology in those remaining non tangle-bearing cholinergic neurons, which project to the hippocampus and cortex in AD (Chan Palay et al, 1988; Mufson et al, 1993; Bowser et al 1997).…”

Section: Hippocampal Plasticity and Brain Reservementioning

confidence: 99%

Hippocampal plasticity during the progression of Alzheimer’s disease

et al. 2015

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Neuroplasticity involves molecular changes in central nervous system (CNS) synaptic structure and function throughout life. The concept of neural organization allows for synaptic remodeling as a compensatory mechanism to the early pathobiology of Alzheimer’s disease (AD) in an attempt to maintain brain function and cognition during the onset of dementia. The hippocampus, a crucial component of the medial temporal lobe memory circuit, is affected early in AD and displays synaptic and intraneuronal molecular remodeling against a pathological background of extracellular amyloid-beta (Aβ) deposition and intracellular neurofibrillary tangle (NFT) formation in the early stages of AD. Here we discuss human clinical pathological findings supporting the concept that the hippocampus is capable of neural plasticity during mild cognitive impairment (MCI), a prodromal stage of AD and early stage AD.

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Section: Hippocampal Plasticity and Brain Reservementioning

confidence: 99%

Hippocampal plasticity during the progression of Alzheimer’s disease

et al. 2015

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“…GSK‐3β is dephosphorylated at Ser9 by PP2A . PP2A is the major phosphatase that accounts for > 70% tau phosphatase activity in human brain .…”

Section: Discussionmentioning

confidence: 99%

“…Protein kinase B/AKT, activated by PI3K signaling, phosphorylates GSK‐3β at Ser9 and suppresses its activity . We previously reported that protein phosphatase 2A (PP2A) efficiently dephosphorylates GSK‐3β at Ser9 . Phosphorylation of Ser9 inhibits the cleavage of GSK‐3β by calpain at both N‐ and C termini .…”

mentioning

confidence: 99%

C‐terminal truncation of GSK‐3β enhances its dephosphorylation by PP2A

Jin

Wen

et al. 2017

FEBS Letters

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Glycogen synthase kinase-3β (GSK-3β) is the major tau kinase. Its phosphorylation at Ser9 suppresses the activity. In Alzheimer's disease (AD) brain, GSK-3β is truncated at the C terminus by overactivated calpain I, leading to an increase in its activity. However, the effect of truncation on its phosphorylation is unknown. We found here that in AD brain and in cultured cells, C-terminally truncated GSK-3β is less phosphorylated at Ser9 than the full-length enzyme. The truncation promotes GSK-3β nuclear translocation and enhances its interaction with protein phosphatase 2A (PP2A), leading to dephosphorylation. Thus, the truncation of GSK-3β may enhance its activity through Ser9 dephosphorylation by PP2A. Our findings shed new light on the role of calpain-GSK-3β-PP2A in tau pathogenesis of AD.

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“…Each of these enzymes were isolated from the rat heart during the experiments proposed by Western Blot technique. [32][33][34][35] Regarding the Western Blot analysis, the myocardial tissue must be taken and frozen quickly enough to avoid kinase degradation under the action of the existing proteases from the tissue. To achieve this goal, the heart was excised just before stopping in asystole, rinsed quickly with cold saline solution at 4°C, then suddenly introduced in liquid nitrogen (-196°C).…”

Section: Western-blot Technique For Determining the Kinases Of The Camentioning

confidence: 99%

Cardioprotective Effects Induced by Preconditioning with Halogenated Anesthetics

Păpurică¹,

Săndesc²,

Rogobete³

et al. 2016

Journal of Interdisciplinary Medicine

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backgroundIn the organ transplantation field, a very intense and important topic is to find ways to increase the quality of organs that are taken from willing donors, in order to improve the recovery capacity of the transplant recipients. 1 From the moment of the organ removal until its actual transplantation, there is a variable period of ischemia, named cold-ischemia, responsible for the production Cardioprotective Effects Induced by Preconditioning with Halogenated AnestheticsMarius Papurica 1,2 , Dorel Sandesc 1,2 , Alexandru Florin Rogobete 1,2 , Radu Nartita 3 , Corina Vernic 2 , Sonia Elena Popovici 2 , Ovidiu Horea Bedreag 1,2 1 Clinic of Anesthesia and Intensive Care, "Pius Brinzeu" Emergency County Hospital, Timișoara, Romania 2 Faculty of Medicine, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania 3 Faculty of Chemistry, Biology, Geography, West University of Timișoara, Romania ABSTRACT Background: Numerous studies discuss the protective effects of halogenated anesthetics on myocyte injury induced by the ischemia-reperfusion syndrome of the heart. This mechanism is known as pharmacological preconditioning. Aim of the study: The objective of this study was to identify the effects of two volatile anesthetics frequently used in current clinical practice, Isoflurane and Sevoflurane, on the in situ heart. The study was performed on laboratory animals with induced brain death. Material and methods: The animals were divided into 3 groups, the control group (n = 8), IZO-PRE group (n = 8) and SEVO-PRE group (n = 8), on which the experimental protocol established for this study was applied. From a molecular point of view, the expressions of protein kinase C-epsilon (PKCε) and of glycogen synthase kinase -3 beta (GSK-3β) were investigated. Results: Following the statistical analysis, we observed a significant reduction in the size of the infarcted area in the IZO-PRE group compared to the control group (p <0.0001). Regarding the SEVO-PRE group, no reduction was observed (p >0.05). The expression of GSK-3β is more pronounced in case of the SEVO-PRE group, at 5 minutes after reperfusion, and the effect disappears after 15 minutes. The expression of PKCε as a total form of the enzyme, occurs at 5 minutes after reperfusion in the SEVO-PRE group and late in the IZO-PRE group (after 15 minutes). Conclusions: Both anesthetics that were applied showed a cardioprotective effect. Isoflurane provided a better structural and morphological protection, but Sevoflurane resulted in a more effective protection in terms of functionality, significantly reducing the incidence of extremely severe life-threatening arrhythmias.

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Cross talk between PI3K-AKT-GSK-3β and PP2A pathways determines tau hyperphosphorylation

Cited by 109 publications

References 56 publications

Hippocampal plasticity during the progression of Alzheimer’s disease

Hippocampal plasticity during the progression of Alzheimer’s disease

C‐terminal truncation of GSK‐3β enhances its dephosphorylation by PP2A

Cardioprotective Effects Induced by Preconditioning with Halogenated Anesthetics

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