Targeting GSK3 signaling as a potential therapy of neurodegenerative diseases and aging

References

• Sutherland C. What Are the bona fide GSK3 substrates?. Int J Alzheimers Dis. 2011;2011; ID 505607.
   PubMedGoogle Scholar
• Nagini S, Sophia J, Mishra R. Glycogen synthase kinases: moonlighting proteins with theranostic potential in cancer. Semin Cancer Biol. 2018;
   PubMed Web of Science ®Google Scholar
• Manning BD, Toker A. AKT/PKB signaling: navigating the network. Cell. 2017;169:381–405.
   PubMed Web of Science ®Google Scholar
• Hermida MA, Dinesh Kumar J, Leslie NR. GSK3 and its interactions with the PI3K/AKT/mTOR signalling network. Adv Biol Regul. 2017;65:5–15.
   PubMedGoogle Scholar
• Vallée A, Lecarpentier Y, Guillevin R, et al. Interactions between TGF-β1, canonical WNT/β-catenin pathway and PPAR γ in radiation-induced fibrosis. Oncotarget. 2017;8:90579–90604.
   PubMedGoogle Scholar
• Eldar-Finkelman H, Seger R, Vandenheede JR, et al. Inactivation of glycogen synthase kinase-3 by epidermal growth factor is mediated by mitogen-activated protein kinase/p90 ribosomal protein S6 kinase signaling pathway in NIH/3T3 cells. Journal of Biological Chemistry. 1995;270;3:987–990.
   PubMed Web of Science ®Google Scholar
• Thornton TM, Pedraza-Alva G, Deng B, et al. Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation. Science. 2008;320:667–670.
   PubMed Web of Science ®Google Scholar
• Fang X, Yu SX, Lu Y, et al. Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci U S A. 2000;97:11960–11965.
   PubMed Web of Science ®Google Scholar
• Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: A new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol. 2001;155:505–510.
   PubMed Web of Science ®Google Scholar
• Arevalo M-A, Rodríguez-Tébar A. Activation of casein kinase II and inhibition of phosphatase and tensin homologue deleted on chromosome 10 phosphatase by nerve growth factor/p75 NTR inhibit glycogen synthase kinase-3β and stimulate axonal growth. Mol Biol Cell. 2006;17:3369–3377.
   PubMed Web of Science ®Google Scholar
• Wu G, Huang H, Abreu JG, et al. Inhibition of GSK3 phosphorylation of β-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS One. 2009;4(3):e4926.
   Web of Science ®Google Scholar
• Bennecib M, Gong CX, Grundke-Iqbal I, et al. Role of protein phosphatase-2A and −1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain. FEBS Lett. 2000;485:87–93.
   PubMed Web of Science ®Google Scholar
• Hernández F, Langa E, Cuadros R, et al. Regulation of GSK3 isoforms by phosphatases PP1 and PP2A. Mol Cell Biochem. 2010;344:211–215.
   PubMed Web of Science ®Google Scholar
• Kim Y, Il LY, Seo M, et al. Calcineurin dephosphorylates glycogen synthase kinase-3 beta at serine-9 in neuroblast-derived cells. J Neurochem. 2009;111:344–354.
   PubMed Web of Science ®Google Scholar
• Al-Khouri AM, Ma Y, Togo SH, et al. Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3β. J Biol Chem. 2005;280:35195–35202.
   PubMed Web of Science ®Google Scholar
• Feng Y, Xia Y, Yu G, et al. Cleavage of GSK-3β by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK-3β activity induced by H2O 2. J Neurochem. 2013;126:234–242.
   PubMed Web of Science ®Google Scholar
• Rangel-Barajas C, Coronel I, Florán B. Dopamine receptors and neurodegeneration. Aging Dis. 2015
   PubMed Web of Science ®Google Scholar
• Beaulieu JM. A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health. J Psychiatry Neurosci. 2012;37:7–16.
   PubMed Web of Science ®Google Scholar
• Li X, Zhu W, Roh M-S, et al. In vivo regulation of glycogen synthase kinase-3beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsychopharmacology. 2004
   Web of Science ®Google Scholar
• Polter AM, Yang S, Jope RS, et al. Functional significance of glycogen synthase kinase-3 regulation by serotonin. Cell Signal. 2012
   PubMed Web of Science ®Google Scholar
• O’Brien WT, Huang J, Buccafusca R, et al. Glycogen synthase kinase-3 is essential for β-arrestin-2 complex formation and lithium-sensitive behaviors in mice. J Clin Invest. 2011;121:3756–3762.
   PubMed Web of Science ®Google Scholar
• Xu D, Song R, Wang G, et al. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop. Oncotarget. 2016;7:3427–3439.
   PubMedGoogle Scholar
• Hilioti Z, Gallagher DA, Low-Nam ST, et al. GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs. Genes Dev. 2004;18:35–47.
   PubMed Web of Science ®Google Scholar
• Tullai JW, Tacheva S, Owens LJ, et al. AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. PLoS One. 2011;6
   Web of Science ®Google Scholar
• Hoshi M, Takashima A, Noguchi K, et al. Regulation of mitochondrial pyruvate dehydrogenase activity by tau protein kinase I/glycogen synthase kinase 3beta in brain. Proc Natl Acad Sci U S A. 1996;93:2719–2723.
   PubMed Web of Science ®Google Scholar
• Clayton EL, Sue N, Smillie KJ, et al. Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles. Nat Neurosci. 2010;13:845–851.
   PubMed Web of Science ®Google Scholar
• Uemura K, Kuzuya A, Shimozono Y, et al. GSK3β activity modifies the localization and function of presenilin 1. J Biol Chem. 2007;282:15823–15832.
   PubMed Web of Science ®Google Scholar
• Grimes CA, Jope RS. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem. 2001
   PubMed Web of Science ®Google Scholar
• Wildburger NC, Laezza F. Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase. Front Mol Neurosci. 2012;5:1–15.
   PubMed Web of Science ®Google Scholar
• Tyagarajan SK, Ghosh H, Yevenes GE, et al. Regulation of GABAergic synapse formation and plasticity by GSK3 -dependent phosphorylation of gephyrin. Proc Natl Acad Sci. 2011;108:379–384.
   PubMed Web of Science ®Google Scholar
• Hur EM, Saijilafu, Lee BD, et al. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules. Genes Dev. 2011;25:1968–1981.
   PubMed Web of Science ®Google Scholar
• Scales TME, Lin S, Kraus M, et al. Nonprimed and DYRK1A-primed GSK3 -phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons. J Cell Sci. 2009;122:2424–2435.
   PubMed Web of Science ®Google Scholar
• Sánchez C, Pérez M, Avila J. GSK3β-mediated phosphorylation of the microtubule-associated protein 2C (MAP2C) prevents microtubule bundling. Eur J Cell Biol. 2000;79:252–260.
   PubMed Web of Science ®Google Scholar
• Hergovich A, Lisztwan J, Thoma CR, et al. Priming-dependent phosphorylation and regulation of the tumor suppressor pVHL by glycogen synthase kinase 3. Mol Cell Biol. 2006;26:5784–5796.
   PubMed Web of Science ®Google Scholar
• Yoshimura T, Kawano Y, Arimura N, et al. GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity. Cell. 2005;120:137–149.
   PubMed Web of Science ®Google Scholar
• Alabed YZ, Pool M, Ong Tone S, et al. GSK3 regulates myelin-dependent axon outgrowth inhibition through CRMP4. J Neurosci. 2010;30:5635–5643.
   PubMed Web of Science ®Google Scholar
• Ferrao Santos S, Tasiaux B, Sindic C, et al. Inhibition of neuronal calcium oscillations by cell surface APP phosphorylated on T668. Neurobiol Aging. 2011;32:2308–2313.
   PubMed Web of Science ®Google Scholar
• Hanger DP, Hughes K, Woodgett JR, et al. Glycogen synthase kinase-3 induces Alzheimer’s disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci Lett. 1992;147:58–62.
   PubMed Web of Science ®Google Scholar
• Timm T, Balusamy K, Li X, et al. Glycogen synthase kinase (GSK) 3β directly phosphorylates serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2. J Biol Chem. 2008;283:18873–18882.
   PubMed Web of Science ®Google Scholar
• Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31–39.
   PubMed Web of Science ®Google Scholar
• Bear MF, Abraham WC. Long-term depression in hippocampus. Annu Rev Neurosci. 1996;19:437–462.
   PubMed Web of Science ®Google Scholar
• Mulkey RM, Endo S, Shenolikar S, et al. Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. Nature. 1994;369:486–488.
   PubMed Web of Science ®Google Scholar
• Peineau S, Bradley C, Taghibiglou C, et al. The role of GSK-3 in synaptic plasticity. Br J Pharmacol. 2008;153(Suppl 1):S428–37.
   PubMed Web of Science ®Google Scholar
• Castillo PE, Chiu CQ, Carroll RC. Long-term plasticity at inhibitory synapses. Curr Opin Neurobiol. 2011;21:328–338.
   PubMed Web of Science ®Google Scholar
• Meunier CNJ, Chameau P, Fossier PM. Modulation of synaptic plasticity in the cortex needs to understand all the players. Front Synaptic Neurosci. 2017;9:2.
   PubMedGoogle Scholar
• Dennis SH, Pasqui F, Colvin EM, et al. Activation of muscarinic M1 acetylcholine receptors induces long-term potentiation in the hippocampus. Cereb Cortex. 2016;26:414–426.
   PubMed Web of Science ®Google Scholar
• Bartzokis G. Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments. Neuropharmacology. 2012;62:2137–2153.
   PubMed Web of Science ®Google Scholar
• Beurel E, Grieco SF, Jope RS. Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther. 2015;148:114–131.
   PubMed Web of Science ®Google Scholar
• Gagolewicz PJ, Dringenberg HC. Age-dependent switch of the role of serotonergic 5-HT 1A receptors in gating long-term potentiation in rat visual cortex In Vivo. Neural Plast. 2016;2016:1–11.
   Google Scholar
• Shahidi S, Asl SS, Komaki A, et al. The effect of chronic stimulation of serotonin receptor type 7 on recognition, passive avoidance memory, hippocampal long-term potentiation, and neuronal apoptosis in the amyloid β protein treated rat. Psychopharmacology (Berl). 2018;235:1513–1525.
   PubMed Web of Science ®Google Scholar
• Wang RY, Arvanov VL. M100907, a highly selective 5-HT2A receptor antagonist and a potential atypical antipsychotic drug, facilitates induction of long-term potentiation in area CA1 of the rat hippocampal slice. Brain Res. 1998;779:309–313.
   PubMed Web of Science ®Google Scholar
• Leroy K, Brion JP. Developmental expression and localization of glycogen synthase kinase-3beta in rat brain. J Chem Neuroanat. 1999;16:279–293.
   PubMed Web of Science ®Google Scholar
• Shahab L, Plattner F, Irvine EE, et al. Dynamic range of GSK3α not GSK3β is essential for bidirectional synaptic plasticity at hippocampal CA3-CA1 synapses. Hippocampus. 2014;24:1413–1416.
   PubMed Web of Science ®Google Scholar
• Li Y-C, Yang -S-S, Gao W-J. Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex. Neuropharmacology. 2016;108:403–414.
   PubMed Web of Science ®Google Scholar
• Polter AM, Li X. Glycogen synthase kinase-3 is an intermediate modulator of serotonin neurotransmission. Front Mol Neurosci. 2011;4:31.
   PubMed Web of Science ®Google Scholar
• De Sarno P, Bijur GN, Zmijewska AA, et al. In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors. Neurobiol Aging. 2006;27:413–422.
   PubMed Web of Science ®Google Scholar
• Jiang L, Kosenko A, Yu C, et al. Activation of m1 muscarinic acetylcholine receptor induces surface transport of KCNQ channels through a CRMP-2-mediated pathway. J Cell Sci. 2015;128:4235–4245.
   PubMed Web of Science ®Google Scholar
• Giessel AJ, Sabatini BL. M1 muscarinic receptors boost synaptic potentials and calcium influx in dendritic spines by inhibiting postsynaptic SK channels. Neuron. 2010;68:936–947.
   PubMed Web of Science ®Google Scholar
• Peineau S, Taghibiglou C, Bradley C, et al. LTP inhibits LTD in the hippocampus via regulation of GSK3β. Neuron. 2007;53:703–717.
   PubMed Web of Science ®Google Scholar
• Mt M-P, Gomez-Villafuertes R, Gualix J, et al. Nucleotides in neuroregeneration and neuroprotection. Neuropharmacology. 2016;104:243–254.
   PubMed Web of Science ®Google Scholar
• Chew B, Ryu JR, Ng T, et al. Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity. Front Behav Neurosci. 2015;9:158.
   PubMed Web of Science ®Google Scholar
• Zhu L-Q, Wang S-H, Liu D, et al. Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments. J Neurosci. 2007;27:12211–12220.
   PubMed Web of Science ®Google Scholar
• Pardo M, Abrial E, Jope RS, et al. GSK3β isoform-selective regulation of depression, memory and hippocampal cell proliferation. Genes, Brain Behav. 2016;15:348–355.
   PubMed Web of Science ®Google Scholar
• Ochs SM, Dorostkar MM, Aramuni G, et al. Loss of neuronal GSK3β reduces dendritic spine stability and attenuates excitatory synaptic transmission via β-catenin. Mol Psychiatry. 2015;20:482–489.
   PubMed Web of Science ®Google Scholar
• Gozdz A, Nikolaienko O, Urbanska M, et al. GSK3α and GSK3β phosphorylate Arc and regulate its degradation. Front Mol Neurosci. 2017;10:192.
   PubMed Web of Science ®Google Scholar
• Petrini EM, Ravasenga T, Hausrat TJ, et al. Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. Nat Commun. 2014;5:3921.
   PubMed Web of Science ®Google Scholar
• Zhu L-Q, Liu D, Hu J, et al. GSK-3 beta inhibits presynaptic vesicle exocytosis by phosphorylating P/Q-type calcium channel and interrupting SNARE complex formation. J Neurosci. 2010;30:3624–3633.
   PubMed Web of Science ®Google Scholar
• King MK, Pardo M, Cheng Y, et al. Glycogen synthase kinase-3 inhibitors: rescuers of cognitive impairments. Pharmacol Ther. 2014;141:1–12.
   PubMed Web of Science ®Google Scholar
• Maqbool M, Mobashir M, Hoda N. Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer’s disease. Eur J Med Chem. 2016;107:63–81.
   PubMed Web of Science ®Google Scholar
• Suzuki A, Stern SA, Bozdagi O, et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 2011;144:810–823.
   PubMed Web of Science ®Google Scholar
• Drulis-Fajdasz D, Wójtowicz T, Wawrzyniak M, et al. Involvement of cellular metabolism in age-related LTP modifications in rat hippocampal slices. Oncotarget. 2015;6:14065–14081.
   PubMedGoogle Scholar
• Silva T, Reis J, Teixeira J, et al. Alzheimer’s disease, enzyme targets and drug discovery struggles: from natural products to drug prototypes. Ageing Res Rev. 2014;15:116–145.
   PubMed Web of Science ®Google Scholar
• Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol. 2007;8:101–112.
   PubMed Web of Science ®Google Scholar
• Morroni F, Sita G, Tarozzi A, et al. Early effects of Aβ1-42 oligomers injection in mice: involvement of PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways. Behav Brain Res. 2016;314:106–115.
   PubMed Web of Science ®Google Scholar
• Yi JH, Baek SJ, Heo S, et al. Direct pharmacological Akt activation rescues Alzheimer’s disease like memory impairments and aberrant synaptic plasticity. Neuropharmacology. 2018;128:282–292.
   PubMed Web of Science ®Google Scholar
• Zhang Z-X, Zhao R-P, Wang D-S, et al. Fuzhisan ameliorates Aβ production and tau phosphorylation in hippocampal of 11 month old APP/PS1 transgenic mice: A western blot study. Exp Gerontol. 2016;84:88–95.
   PubMed Web of Science ®Google Scholar
• Deng Y, Xiong Z, Chen P, et al. β-Amyloid impairs the regulation of N-methyl-D-aspartate receptors by glycogen synthase kinase 3. Neurobiol Aging. 2014;35:449–459.
   PubMed Web of Science ®Google Scholar
• Tajes M, Gutierrez-Cuesta J, Folch J, et al. Lithium treatment decreases activities of tau kinases in a murine model of senescence. J Neuropathol Exp Neurol. 2008;67:612–623.
   PubMed Web of Science ®Google Scholar
• Hampel H, Ewers M, Bürger K, et al. Lithium trial in Alzheimer’s disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 2009;70:922–931.
   PubMed Web of Science ®Google Scholar
• Bao X-Q, Li N, Wang T, et al. FLZ alleviates the memory deficits in transgenic mouse model of Alzheimer’s disease via decreasing beta-amyloid production and tau hyperphosphorylation. PLoS One. 2013;8:e78033.
   PubMed Web of Science ®Google Scholar
• Prati F, De Simone A, Bisignano P, et al. Multitarget drug discovery for Alzheimer’s Disease: triazinones as BACE-1 and GSK-3β inhibitors. Angew Chemie Int Ed. 2015;54:1578–1582.
   PubMed Web of Science ®Google Scholar
• Domínguez JM, Fuertes A, Orozco L, et al. Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3β by Tideglusib. J Biol Chem. 2012;287:893–904.
   PubMed Web of Science ®Google Scholar
• Serenó L, Coma M, Rodríguez M, et al. A novel GSK-3β inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009;35:359–367.
   PubMed Web of Science ®Google Scholar
• Del Ser T, Steinwachs KC, Gertz HJ, et al. Treatment of Alzheimer’s disease with the GSK-3 inhibitor tideglusib: a pilot study. J Alzheimer’s Dis. 2012;33:205–215.
   Web of Science ®Google Scholar
• Dey A, Hao S, Wosiski-Kuhn M, et al. Glucocorticoid-mediated activation of GSK3β promotes tau phosphorylation and impairs memory in type 2 diabetes. Neurobiol Aging. 2017;57:75–83.
   PubMed Web of Science ®Google Scholar
• Lange C, Mix E, Frahm J, et al. Small molecule GSK-3 inhibitors increase neurogenesis of human neural progenitor cells. Neurosci Lett. 2011;488:36–40.
   PubMed Web of Science ®Google Scholar
• Petit-Paitel A, Brau F, Cazareth J, et al. Involvment of cytosolic and mitochondrial GSK-3β in mitochondrial dysfunction and neuronal cell death of MPTP/MPP+-treated neurons. PLoS One. 2009;4:e5491.
   PubMed Web of Science ®Google Scholar
• Cross DA, Culbert AA, Chalmers KA, et al. Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem. 2001;77:94–102.
   PubMed Web of Science ®Google Scholar
• McCubrey JA, Abrams SL, Lertpiriyapong K, et al. Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells—power of nutraceuticals. Adv Biol Regul. 2018;67:190–211.
   PubMedGoogle Scholar
• Turner RS, Thomas RG, Craft S, et al. Alzheimer’s Disease cooperative study. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85:1383–1391.
   PubMed Web of Science ®Google Scholar
• Durairajan SSK, Liu L-F, Lu J-H, et al. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model. Neurobiol Aging. 2012;33:2903–2919.
   PubMed Web of Science ®Google Scholar
• Goñi-Oliver P, Avila J, Hernández F. Memantine inhibits calpain-mediated truncation of GSK-3 Induced by NMDA: implications in Alzheimer’s Disease. J Alzheimer’s Dis. 2009;18:843–848.
   PubMed Web of Science ®Google Scholar
• Tayeb HO, Yang HD, Price BH, et al. Pharmacotherapies for Alzheimer’s disease: beyond cholinesterase inhibitors. Pharmacol Ther. 2012;134:8–25.
   PubMed Web of Science ®Google Scholar
• Noh M-Y, Koh S-H, Kim Y, et al. Neuroprotective effects of donepezil through inhibition of GSK-3 activity in amyloid-β-induced neuronal cell death. J Neurochem. 2009;108:1116–1125.
   PubMed Web of Science ®Google Scholar
• Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015;386:896–912.
   PubMed Web of Science ®Google Scholar
• DeMaagd G, Philip A. Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P T. 2015;40:504–532.
   PubMedGoogle Scholar
• Nagao M, Hayashi H. Glycogen synthase kinase-3beta is associated with Parkinson’s disease. Neurosci Lett. 2009;449:103–107.
   PubMed Web of Science ®Google Scholar
• Hernandez-Baltazar D, Mendoza-Garrido ME, Martinez-Fong D. Activation of GSK-3β and caspase-3 occurs in nigral dopamine neurons during the development of apoptosis activated by a striatal injection of 6-hydroxydopamine. PLoS One. 2013;8:e70951.
   PubMed Web of Science ®Google Scholar
• Pandey MK, DeGrado TR. Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics. 2016;6:571–593.
   PubMed Web of Science ®Google Scholar
• Ren Z-X, Zhao Y-F, Cao T, et al. Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson’s disease by suppressing glycogen synthase kinase-3 beta activity. Acta Pharmacol Sin. 2016;37:1315–1324.
   PubMed Web of Science ®Google Scholar
• Wang W, Yang Y, Ying C, et al. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology. 2007;52:1678–1684.
   PubMed Web of Science ®Google Scholar
• Morales-García JA, Susín C, Alonso-Gil S, et al. Glycogen synthase kinase-3 inhibitors as potent therapeutic agents for the treatment of Parkinson disease. ACS Chem Neurosci. 2013;4:350–360.
   PubMed Web of Science ®Google Scholar
• Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. Lancet. 1989;1:1269.
   PubMed Web of Science ®Google Scholar
• Moon HE, Paek SH. Mitochondrial dysfunction in Parkinson’s Disease. Exp Neurobiol. 2015;24:103–116.
   PubMed Web of Science ®Google Scholar
• Linseman DA, Butts BD, Precht TA, et al. Glycogen synthase kinase-3beta phosphorylates bax and promotes its mitochondrial localization during neuronal apoptosis. J Neurosci. 2004;24:9993–10002.
   PubMed Web of Science ®Google Scholar
• Engelender S, Kaminsky Z, Guo X, et al. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat Genet. 1999;22:110–114.
   PubMed Web of Science ®Google Scholar
• Credle JJ, George JL, Wills J, et al. GSK-3β dysregulation contributes to Parkinson’s-like pathophysiology with associated region-specific phosphorylation and accumulation of tau and α-synuclein. Cell Death Differ. 2015;22:838–851.
   PubMed Web of Science ®Google Scholar
• Kim WS, Kågedal K, Halliday GM. Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther. 2014;6:73.
   PubMed Web of Science ®Google Scholar
• Perez RG, Waymire JC, Lin E, et al. A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci. 2002;22:3090–3099.
   PubMed Web of Science ®Google Scholar
• Colla E, Jensen PH, Pletnikova O, et al. Accumulation of toxic α-synuclein oligomer within endoplasmic reticulum occurs in α-synucleinopathy in vivo. J Neurosci. 2012;32:3301–3305.
   PubMed Web of Science ®Google Scholar
• Song L, De Sarno P, Jope RS. Central role of glycogen synthase kinase-3beta in endoplasmic reticulum stress-induced caspase-3 activation. J Biol Chem. 2002;277:44701–44708.
   PubMed Web of Science ®Google Scholar
• Avraham E, Szargel R, Eyal A, et al. Glycogen synthase kinase 3beta modulates synphilin-1 ubiquitylation and cellular inclusion formation by SIAH: implications for proteasomal function and Lewy body formation. J Biol Chem. 2005;280:42877–42886.
   PubMed Web of Science ®Google Scholar
• Beaulieu J-M, Sotnikova TD, Yao W-D, et al. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci. 2004;101:5099–5104.
   PubMed Web of Science ®Google Scholar
• Li X, Rosborough KM, Friedman AB, et al. Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int J Neuropsychopharmacol. 2007;10:7–19.
   PubMed Web of Science ®Google Scholar
• Lim JH, Kim K-M, Kim SW, et al. Bromocriptine activates NQO1 via Nrf2-PI3K/Akt signaling: novel cytoprotective mechanism against oxidative damage. Pharmacol Res. 2008;57:325–331.
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association. DSM-5 Task Force. Diagnostic and statistical manual of mental disorders : DSM-5. American Psychiatric Association (Washington, D.C.);2013. p. 947.
   Google Scholar
• Saha S, Chant D, Welham J, et al. A Systematic Review of the Prevalence of Schizophrenia. Hyman SE, editor. PLoS Med. 2005;2:e141.
   PubMed Web of Science ®Google Scholar
• Misiak B, Stramecki F, Gawęda Ł, et al. Interactions between variation in candidate genes and environmental factors in the etiology of schizophrenia and bipolar disorder: a systematic review. Mol Neurobiol. 2018;55:5075–5100.
   PubMed Web of Science ®Google Scholar
• Robinson DG. Pharmacological treatments for first-episode schizophrenia. Schizophr Bull. 2005;31:705–722.
   PubMed Web of Science ®Google Scholar
• Beaulieu J-M, Gainetdinov RR, Caron MG. Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol. 2009;49:327–347.
   PubMed Web of Science ®Google Scholar
• Tamura M, Mukai J, Gordon JA, et al. Developmental inhibition of Gsk3 rescues behavioral and neurophysiological deficits in a mouse model of schizophrenia predisposition. Neuron. 2016;89:1100–1109.
   PubMed Web of Science ®Google Scholar
• Mao Y, Ge X, Frank CL, et al. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling. Cell. 2009;136:1017–1031.
   PubMed Web of Science ®Google Scholar
• Abdel-Aleem GA, Khaleel EF, Mostafa DG, et al. Neuroprotective effect of resveratrol against brain ischemia reperfusion injury in rats entails reduction of DJ-1 protein expression and activation of PI3K/Akt/GSK3b survival pathway. Arch Physiol Biochem. 2016;122:200–213.
   PubMed Web of Science ®Google Scholar
• Magaji MG, Iniaghe LO, Abolarin M, et al. Neurobehavioural evaluation of resveratrol in murine models of anxiety and schizophrenia. Metab Brain Dis. 2017;32:437–442.
   PubMed Web of Science ®Google Scholar
• Zortea K, Franco VC, Guimarães P, et al. Resveratrol supplementation did not improve cognition in patients with schizophrenia: results from a randomized clinical trial. Front Psychiatry. 2016;7:159.
   PubMed Web of Science ®Google Scholar
• Hu S, Begum AN, Jones MR, et al. GSK3 inhibitors show benefits in an Alzheimer’s disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis. 2009;33:193–206.
   PubMed Web of Science ®Google Scholar
• Eldar-Finkelman H, Martinez A. GSK-3 inhibitors: preclinical and clinical focus on CNS. Front Mol Neurosci. 2011;4:32.
   PubMed Web of Science ®Google Scholar
• O’Brien WT, Harper AD, Jové F, et al. Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium. J Neurosci. 2004;24:6791–6798.
   PubMed Web of Science ®Google Scholar
• Prickaerts J, Moechars D, Cryns K, et al. Transgenic mice overexpressing glycogen synthase kinase 3beta: a putative model of hyperactivity and mania. J Neurosci. 2006;26:9022–9029.
   PubMed Web of Science ®Google Scholar
• Kozlovsky N, Shanon-Weickert C, Tomaskovic-Crook E, et al. Reduced GSK-3beta mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients. J Neural Transm. 2004;111:1583–1592.
   PubMed Web of Science ®Google Scholar
• Kozlovsky N, Regenold WT, Levine J, et al. GSK-3beta in cerebrospinal fluid of schizophrenia patients. J Neural Transm. 2004;111:1093–1098.
   PubMed Web of Science ®Google Scholar
• Kozlovsky N, Belmaker RH, Agam G. Low GSK-3 activity in frontal cortex of schizophrenic patients. Schizophr Res. 2001;52:101–105.
   PubMed Web of Science ®Google Scholar
• Nadri C, Dean B, Scarr E, et al. GSK-3 parameters in postmortem frontal cortex and hippocampus of schizophrenic patients. Schizophr Res. 2004;71:377–382.
   PubMed Web of Science ®Google Scholar
• Beasley C, Cotter D, Khan N, et al. Glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal cortex in schizophrenia. Neurosci Lett. 2001;302:117–120.
   PubMed Web of Science ®Google Scholar
• Beasley C, Cotter D, Everall I. An investigation of the Wnt-signalling pathway in the prefrontal cortex in schizophrenia, bipolar disorder and major depressive disorder. Schizophr Res. 2002;58:63–67.
   PubMed Web of Science ®Google Scholar
• Emamian ES, Hall D, Birnbaum MJ, et al. Convergent evidence for impaired AKT1-GSK3β signaling in schizophrenia. Nat Genet. 2004;36:131–137.
   PubMed Web of Science ®Google Scholar
• Joaquim HPG, Zanetti MV, Serpa MH, et al. Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis. Schizophr Res. 2018;195:402–405.
   PubMed Web of Science ®Google Scholar
• Ricci A, Bronzetti E, Mannino F, et al. Dopamine receptors in human platelets. Naunyn Schmiedebergs Arch Pharmacol. 2001;363:376–382.
   PubMed Web of Science ®Google Scholar
• Honea R, Crow TJ, Passingham D, et al. Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry. 2005;162:2233–2245.
   PubMed Web of Science ®Google Scholar
• Glantz LA, Gilmore JH, Lieberman JA, et al. Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res. 2006;81:47–63.
   PubMed Web of Science ®Google Scholar
• Beurel E, Jope RS. The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog Neurobiol. 2006;79:173–189.
   PubMed Web of Science ®Google Scholar
• Wexler EM, Rosen E, Lu D, et al. Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways. Sci Signal. 2011;4:ra65–ra65.
   PubMed Web of Science ®Google Scholar
• Dobson-Stone C, Polly P, Korgaonkar MS, et al. GSK3B and MAPT polymorphisms are associated with grey matter and intracranial volume in healthy individuals. PLoS One. 2013;8:e71750.
   PubMed Web of Science ®Google Scholar
• Mortimer JA, Snowdon DA, Markesbery WR. Head circumference, education and risk of dementia: findings from the nun study. J Clin Exp Neuropsychol (Neuropsychology Dev Cogn Sect A). 2003;25:671–679.
   PubMed Web of Science ®Google Scholar
• Hu J-H, Zhang H, Wagey R, et al. Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord. J Neurochem. 2003;85:432–442.
   PubMed Web of Science ®Google Scholar
• Yang W, Leystra-Lantz C, Strong MJ. Upregulation of GSK3β expression in frontal and temporal cortex in ALS with cognitive impairment (ALSci). Brain Res. 2008;1196:131–139.
   PubMed Web of Science ®Google Scholar
• Sreedharan J, Neukomm LJ, Brown RH, et al. Age-dependent TDP-43-mediated motor neuron degeneration requires GSK3, hat-trick, and xmas-2. Curr Biol. 2015;25:2130–2136.
   PubMed Web of Science ®Google Scholar
• Shen Q, Wang X, Chen Y, et al. Expression QTL and regulatory network analysis of microtubule-associated protein tau gene. Parkinsonism Relat Disord. 2009;15:525–531.
   PubMed Web of Science ®Google Scholar
• Mines MA, Yuskaitis CJ, King MK, et al. GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and Autism. PLoS One. 2010;5:e9706.
   PubMed Web of Science ®Google Scholar
• Adli M, Hollinde DL, Stamm T, et al. Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-Beta −50T/C single nucleotide polymorphism. Biol Psychiatry. 2007;62:1295–1302.
   PubMed Web of Science ®Google Scholar
• Martin M, Rehani K, Jope RS, et al. Toll-like receptor–mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol. 2005;6:777–784.
   PubMed Web of Science ®Google Scholar
• Beurel E, Yeh W-I, Michalek SM, et al. Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 Cells. J Immunol. 2011;186:1391–1398.
   PubMed Web of Science ®Google Scholar
• Bianchi M, De Lucchini S, Marin O, et al. Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1 during cell spreading and migration. Biochem J. 2005;391:359–370.
   PubMed Web of Science ®Google Scholar
• de Melker AA, Desban N, Duband J-L. Cellular localization and signaling activity of β-catenin in migrating neural crest cells. Dev Dyn. 2004;230:708–726.
   PubMed Web of Science ®Google Scholar
• Etienne-Manneville S, Hall A. Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity. Nature. 2003;421:753–756.
   PubMed Web of Science ®Google Scholar
• Licinio J, Wong ML. The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry. 1999;4:317–327.
   PubMed Web of Science ®Google Scholar
• Block ML, Hong J-S. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77–98.
   PubMed Web of Science ®Google Scholar
• Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000;21:383–421.
   PubMedGoogle Scholar
• Akiyama H, Mori H, Saido T, et al. Occurrence of the diffuse amyloid β-protein (Aβ) deposits with numerous Aβ-containing glial cells in the cerebral cortex of patients with Alzheimer’s disease. Glia. 1999;25:324–331.
   PubMed Web of Science ®Google Scholar
• Brochard V, Combadière B, Prigent A, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2008;119:182–192.
   PubMed Web of Science ®Google Scholar
• Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. 2016;53:1181–1194.
   PubMed Web of Science ®Google Scholar
• Park C, Lee S, Cho I-H, et al. TLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expression. Glia. 2006;53:248–256.
   PubMed Web of Science ®Google Scholar
• Yuskaitis CJ, Jope RS. Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity. Cell Signal. 2009;21:264–273.
   PubMed Web of Science ®Google Scholar
• Peña-Altamira E, Petralla S, Massenzio F, et al. Nutritional and pharmacological strategies to regulate microglial polarization in cognitive aging and Alzheimer’s Disease. Front Aging Neurosci. 2017;9:175.
   PubMed Web of Science ®Google Scholar
• Beurel E, Jope RS. Differential regulation of STAT family members by glycogen synthase kinase-3. J Biol Chem. 2008;283:21934–21944.
   PubMed Web of Science ®Google Scholar
• Cao Q, Karthikeyan A, Dheen ST, et al. Production of proinflammatory mediators in activated microglia is synergistically regulated by Notch-1, glycogen synthase kinase (GSK-3β) and NF-κB/p65 signalling. PLoS One. 2017;12:e0186764.
   PubMed Web of Science ®Google Scholar
• Kim DW, Lee JH, Park SK, et al. Astrocytic expressions of phosphorylated Akt, GSK3β and CREB following an excitotoxic lesion in the mouse hippocampus. Neurochem Res. 2007;32:1460–1468.
   PubMed Web of Science ®Google Scholar
• Wang M-J, Huang H-Y, Chen W-F, et al. Glycogen synthase kinase-3β inactivation inhibits tumor necrosis factor-α production in microglia by modulating nuclear factor κB and MLK3/JNK signaling cascades. J Neuroinflammation. 2010;7:99.
   PubMed Web of Science ®Google Scholar
• Nahman S, Belmaker R, Azab AN. Effects of lithium on lipopolysaccharide-induced inflammation in rat primary glia cells. Innate Immun. 2012;18:447–458.
   PubMed Web of Science ®Google Scholar
• Licht-Murava A, Paz R, Vaks L, et al. A unique type of GSK-3 inhibitor brings new opportunities to the clinic. Sci Signal Am Assoc Adv Sci. 2016;9:ra110.
   PubMed Web of Science ®Google Scholar
• Haroutunian V, Katsel P, Roussos P, et al. Myelination, oligodendrocytes, and serious mental illness. Glia. 2014;62:1856–1877.
   PubMed Web of Science ®Google Scholar
• Wyss-Coray T, Loike JD, Brionne TC, et al. Adult mouse astrocytes degrade amyloid-β in vitro and in situ. Nat Med. 2003;9:453–457.
   PubMed Web of Science ®Google Scholar
• Gibbs M. Reflections on glycogen and β-amyloid: why does glycogenolytic β2-adrenoceptor stimulation not rescue memory after β-amyloid? Metab Brain Dis. 2015;30:345–352.
   PubMed Web of Science ®Google Scholar
• McCubrey JA, Lertpiriyapong K, Steelman LS, et al. Regulation of GSK-3 activity by curcumin, berberine and resveratrol: potential effects on multiple diseases. Adv Biol Regul. 2017;65:77–88.
   PubMedGoogle Scholar
• Drulis-Fajdasz D, Rakus D, Wiśniewski JR, et al. Systematic analysis of GSK-3 signaling pathways in aging of cerebral tissue. Adv Biol Regul. 2018;69:35–42.
   PubMedGoogle Scholar
• Drulis-Fajdasz D, Gizak A, Wójtowicz T, et al. Aging-associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte-to-neuron lactate shuttle. Glia. 2018;66:1481–1495.
   PubMed Web of Science ®Google Scholar