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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

GSK-3β and its Inhibitors in Alzheimer's Disease: A Recent Update

Author(s): Neha Chauhan, Swati Paliwal, Smita Jain, Kanika Verma, Sarvesh Paliwal and Swapnil Sharma*

Volume 22, Issue 22, 2022

Published on: 18 August, 2022

Page: [2881 - 2895] Pages: 15

DOI: 10.2174/1389557522666220420094317

Price: $65

Abstract

Alzheimer’s disease (AD) is an emerging major health and socioeconomic burden worldwide. It is characterized by neuronal loss, memory loss and cognitive impairment in the aging population. Despite several scientific advancements over the past five decades, the underlying molecular mechanism of the disease progression is yet unknown. Glycogen synthase kinase-3β (GSK-3β) has huge implications on the brain function, causing molecular pathologies, neuronal damage and impairment of brain performance in AD. It is one of the key players in signaling pathways for normal brain functioning and a critical molecular link between amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs). GSK-3β activation is driven by phosphorylation of tau(τ) protein which results in disruption of neuronal synaptic activities and the formation of neuronal plaques. Although the accumulation of Aβ plaques and intracellular tangles of hyperphosphorylated tau protein has been well established as neuropathological hallmarks of the disease, the molecular mechanism has not been unraveled. This review focuses on the role of GSK-3β in the molecular mechanisms participating in the manifestation and progression of AD. The review also suggests that GSK-3β inhibitors can be used as potential therapeutic targets for amelioration of AD.

Keywords: Alzheimer’s disease, glycogen synthase kinase-3, neurodegenerative diseases, neurofibrillary tangles, tau protein, amyloid-beta.

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[1]
Zilberzwige-Tal, S.; Gazit, E. Go with the flow microfluidics approaches for amyloid research. Chem. Asian J., 2018, 13(22), 3437-3447.
[http://dx.doi.org/10.1002/asia.201801007] [PMID: 30117682]
[2]
Livingston, G.; Huntley, J.; Sommerlad, A.; Ames, D.; Ballard, C.; Banerjee, S.; Brayne, C.; Burns, A.; Cohen-Mansfield, J.; Cooper, C.; Costafreda, S.G.; Dias, A.; Fox, N.; Gitlin, L.N.; How-ard, R.; Kales, H.C.; Kivimäki, M.; Larson, E.B.; Ogunniyi, A.; Orgeta, V.; Ritchie, K.; Rockwood, K.; Sampson, E.L.; Samus, Q.; Schneider, L.S.; Selbæk, G.; Teri, L.; Mukadam, N. Dementia preven-tion, intervention, and care: 2020 report of the Lancet Commission. Lancet, 2020, 396(10248), 413-446.
[http://dx.doi.org/10.1016/S0140-6736(20)30367-6] [PMID: 32738937]
[3]
Zhang, X.X.; Tian, Y.; Wang, Z.T.; Ma, Y.H.; Tan, L.; Yu, J.T. The epidemiology of Alzheimer’s disease modifiable risk factors and prevention. J. Prev. Alzheimers Dis., 2021, 8(3), 313-321.
[PMID: 34101789]
[4]
Mamun, A.A.; Uddin, M.S.; Mathew, B.; Ashraf, G.M. Toxic tau: Structural origins of tau aggre-gation in Alzheimer’s disease. Neural Regen. Res., 2020, 15(8), 1417-1420.
[http://dx.doi.org/10.4103/1673-5374.274329] [PMID: 31997800]
[5]
Hoffmeister, L.; Diekmann, M.; Brand, K.; Huber, R. GSK3: A kinase balancing promotion and resolution of inflammation. Cells, 2020, 9(4), 820.
[http://dx.doi.org/10.3390/cells9040820] [PMID: 32231133]
[6]
Forde, J.E.; Dale, T.C. Glycogen synthase kinase 3: A key regulator of cellular fate. Cell. Mol. Life Sci., 2007, 64(15), 1930-1944.
[http://dx.doi.org/10.1007/s00018-007-7045-7] [PMID: 17530463]
[7]
Mucke, L.; Selkoe, D.J. Neurotoxicity of amyloid β-protein: Synaptic and network dysfunction. Cold Spring Harb. Perspect. Med., 2012, 2(7), a006338.
[http://dx.doi.org/10.1101/cshperspect.a006338] [PMID: 22762015]
[8]
Huang, L.K.; Chao, S.P.; Hu, C.J. Clinical trials of new drugs for Alzheimer disease. J. Biomed. Sci., 2020, 27(1), 18.
[http://dx.doi.org/10.1186/s12929-019-0609-7] [PMID: 31906949]
[9]
Luo, J. The role of GSK3beta in the development of the central nervous system. Front. Biol. (Beijing), 2012, 7(3), 212-220.
[http://dx.doi.org/10.1007/s11515-012-1222-2] [PMID: 25688261]
[10]
Itoh, S.; Saito, T.; Hirata, M.; Ushita, M.; Ikeda, T.; Woodgett, J.R.; Algül, H.; Schmid, R.M.; Chung, U.I.; Kawaguchi, H. GSK-3α and GSK-3β proteins are involved in early stages of chondro-cyte differentiation with functional redundancy through RelA protein phosphorylation. J. Biol. Chem., 2012, 287(35), 29227-29236.
[http://dx.doi.org/10.1074/jbc.M112.372086] [PMID: 22761446]
[11]
Kisoh, K.; Hayashi, H.; Itoh, T.; Asada, M.; Arai, M.; Yuan, B.; Tanonaka, K.; Takagi, N. In-volvement of GSK-3β phosphorylation through PI3-K/Akt in cerebral ischemia-induced neurogenesis in rats. Mol. Neurobiol., 2017, 54(10), 7917-7927.
[http://dx.doi.org/10.1007/s12035-016-0290-8] [PMID: 27866373]
[12]
Alonso, A.; Zaidi, T.; Novak, M.; Grundke-Iqbal, I.; Iqbal, K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA, 2001, 98(12), 6923-6928.
[http://dx.doi.org/10.1073/pnas.121119298] [PMID: 11381127]
[13]
Noble, W.; Hanger, D.P.; Miller, C.C.J.; Lovestone, S. The importance of tau phosphorylation for neurodegenerative diseases. Front. Neurol., 2013, 4, 83.
[http://dx.doi.org/10.3389/fneur.2013.00083] [PMID: 23847585]
[14]
Mroczko, B.; Groblewska, M.; Litman-Zawadzka, A. The role of protein misfolding and tau oli-gomers (TauOs) in Alzheimer’s disease (AD). Int. J. Mol. Sci., 2019, 20(19), 1-26.
[http://dx.doi.org/10.3390/ijms20194661] [PMID: 31547024]
[15]
Murphy, M.P.; LeVine, H., III Alzheimer’s disease and the amyloid-β peptide. J. Alzheimers Dis., 2010, 19(1), 311-323.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[16]
DeTure, M.A.; Dickson, D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener., 2019, 14(1), 32.
[http://dx.doi.org/10.1186/s13024-019-0333-5] [PMID: 31375134]
[17]
Singh, S.K.; Srivastav, S.; Yadav, A.K.; Srikrishna, S.; Perry, G. Overview of Alzheimer’s dis-ease and some therapeutic approaches targeting Aβ by using several synthetic and herbal compounds. Oxid. Med. Cell. Longev., 2016, 2016(2), 7361613.
[PMID: 27034741]
[18]
Chen, G.F.; Xu, T.H.; Yan, Y.; Zhou, Y.R.; Jiang, Y.; Melcher, K.; Xu, H.E. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol. Sin., 2017, 38(9), 1205-1235.
[http://dx.doi.org/10.1038/aps.2017.28] [PMID: 28713158]
[19]
Wolfe, M.S. The role of tau in neurodegenerative diseases and its potential as a therapeutic tar-get. Scientifica (Cairo), 2012, 2012, 796024.
[http://dx.doi.org/10.6064/2012/796024] [PMID: 24278740]
[20]
Hur, E.M.; Zhou, F.Q. GSK3 signalling in neural development. Nat. Rev. Neurosci., 2010, 11(8), 539-551.
[http://dx.doi.org/10.1038/nrn2870] [PMID: 20648061]
[21]
Jaworski, T.; Banach-Kasper, E.; Gralec, K. GSK-3 β at the intersection of neuronal plasticity and neurodegeneration. Neural Plast., 2019, 2019, 4209475.
[http://dx.doi.org/10.1155/2019/4209475] [PMID: 31191636]
[22]
Giese, K.P. GSK-3: A key player in neurodegeneration and memory. IUBMB Life, 2009, 61(5), 516-521.
[http://dx.doi.org/10.1002/iub.187] [PMID: 19391164]
[23]
Hanger, D.P.; Anderton, B.H.; Noble, W. Tau phosphorylation: the therapeutic challenge for neu-rodegenerative disease. Trends Mol. Med., 2009, 15(3), 112-119.
[http://dx.doi.org/10.1016/j.molmed.2009.01.003] [PMID: 19246243]
[24]
Lauretti, E.; Dincer, O.; Praticò, D. Glycogen synthase kinase-3 signaling in Alzheimer’s disease. Biochim. Biophys. Acta Mol. Cell Res., 2020, 1867(5), 118664.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118664] [PMID: 32006534]
[25]
Medina, M.; Garrido, J.J.; Wandosell, F.G. Modulation of GSK-3 as a therapeutic strategy on tau pathologies. Front. Mol. Neurosci., 2011, 4, 24.
[http://dx.doi.org/10.3389/fnmol.2011.00024] [PMID: 22007157]
[26]
Kremer, A.; Louis, J.V.; Jaworski, T.; Van Leuven, F. GSK3 and Alzheimer’s disease: Facts and fiction. Front. Mol. Neurosci., 2011, 4, 17.
[http://dx.doi.org/10.3389/fnmol.2011.00017] [PMID: 21904524]
[27]
Uemura, K.; Kuzuya, A.; Shimozono, Y.; Aoyagi, N.; Ando, K.; Shimohama, S.; Kinoshita, A. GSK3beta activity modifies the localization and function of presenilin 1. J. Biol. Chem., 2007, 282(21), 15823-15832.
[http://dx.doi.org/10.1074/jbc.M610708200] [PMID: 17389597]
[28]
Magdesian, M.H.; Carvalho, M.M.V.F.; Mendes, F.A.; Saraiva, L.M.; Juliano, M.A.; Juliano, L.; Garcia-Abreu, J.; Ferreira, S.T. Amyloid-β binds to the extracellular cysteine-rich domain of Frizzled and inhibits Wnt/β-catenin signaling. J. Biol. Chem., 2008, 283(14), 9359-9368.
[http://dx.doi.org/10.1074/jbc.M707108200] [PMID: 18234671]
[29]
Kinney, J.W.; Bemiller, S.M.; Murtishaw, A.S.; Leisgang, A.M.; Salazar, A.M.; Lamb, B.T. In-flammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. (N. Y.), 2018, 4(1), 575-590.
[http://dx.doi.org/10.1016/j.trci.2018.06.014] [PMID: 30406177]
[30]
Spangenberg, E.E.; Green, K.N. Lessons learned from microglia-depletion department of neuro-biology and behavior. Brain Behav. Immun., 2016, 61, 1-11.
[http://dx.doi.org/10.1016/j.bbi.2016.07.003] [PMID: 27395435]
[31]
Green, H.F.; Nolan, Y.M. GSK-3 mediates the release of IL-1β, TNF-α and IL-10 from cortical glia. Neurochem. Int., 2012, 61(5), 666-671.
[http://dx.doi.org/10.1016/j.neuint.2012.07.003] [PMID: 22796213]
[32]
Xavier, I.J.; Mercier, P.A.; McLoughlin, C.M.; Ali, A.; Woodgett, J.R.; Ovsenek, N. Glycogen synthase kinase 3β negatively regulates both DNA-binding and transcriptional activities of heat shock factor 1. J. Biol. Chem., 2000, 275(37), 29147-29152.
[http://dx.doi.org/10.1074/jbc.M002169200] [PMID: 10856293]
[33]
Grimes, C.A.; Jope, R.S. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 β and facilitated by lithium. J. Neurochem., 2001, 78(6), 1219-1232.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00495.x] [PMID: 11579131]
[34]
Gregory, M.A.; Qi, Y.; Hann, S.R. Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J. Biol. Chem., 2003, 278(51), 51606-51612.
[http://dx.doi.org/10.1074/jbc.M310722200] [PMID: 14563837]
[35]
Hooper, C.; Markevich, V.; Plattner, F.; Killick, R.; Schofield, E.; Engel, T.; Hernandez, F.; An-derton, B.; Rosenblum, K.; Bliss, T.; Cooke, S.F.; Avila, J.; Lucas, J.J.; Giese, K.P.; Stephenson, J.; Lovestone, S. Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur. J. Neurosci., 2007, 25(1), 81-86.
[http://dx.doi.org/10.1111/j.1460-9568.2006.05245.x] [PMID: 17241269]
[36]
Pardo, M.; Abrial, E.; Jope, R.S.; Beurel, E. GSK3β isoform-selective regulation of depression, memory and hippocampal cell proliferation. Genes Brain Behav., 2016, 15(3), 348-355.
[http://dx.doi.org/10.1111/gbb.12283] [PMID: 26749572]
[37]
Liao, W.W.; Tsai, S.Y.; Liao, C.C.; Chen, K.B.; Yeh, G.C.; Chen, J.Y.; Wen, Y.R. Coadministra-tion of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced anal-gesic tolerance and withdrawal syndrome. J. Chin. Med. Assoc., 2014, 77(1), 31-37.
[http://dx.doi.org/10.1016/j.jcma.2013.09.008] [PMID: 24176578]
[38]
Cho, J.H.; Johnson, G.V.W. Glycogen synthase kinase 3β phosphorylates tau at both primed and unprimed sites. Differential impact on microtubule binding. J. Biol. Chem., 2003, 278(1), 187-193.
[http://dx.doi.org/10.1074/jbc.M206236200] [PMID: 12409305]
[39]
Frame, S.; Cohen, P.; Biondi, R.M. A common phosphate binding site explains the unique sub-strate specificity of GSK3 and its inactivation by phosphorylation. Mol. Cell, 2001, 7(6), 1321-1327.
[http://dx.doi.org/10.1016/S1097-2765(01)00253-2] [PMID: 11430833]
[40]
Dajani, R.; Fraser, E.; Roe, S.M.; Young, N.; Good, V.; Dale, T.C.; Pearl, L.H. Crystal structure of glycogen synthase kinase 3 beta: Structural basis for phosphate-primed substrate specificity and au-toinhibition. Cell, 2001, 105(6), 721-732.
[http://dx.doi.org/10.1016/S0092-8674(01)00374-9] [PMID: 11440715]
[41]
Congdon, E.E.; Sigurdsson, E.M. Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol., 2018, 14(7), 399-415.
[http://dx.doi.org/10.1038/s41582-018-0013-z] [PMID: 29895964]
[42]
Bulic, B.; Pickhardt, M.; Mandelkow, E. Progress and developments in tau aggregation inhibitors for Alzheimer disease. J. Med. Chem., 2013, 56(11), 4135-4155.
[http://dx.doi.org/10.1021/jm3017317] [PMID: 23484434]
[43]
Mabonga, L.; Kappo, A.P. Protein-protein interaction modulators: Advances, successes and re-maining challenges. Biophys. Rev., 2019, 11(4), 559-581.
[http://dx.doi.org/10.1007/s12551-019-00570-x] [PMID: 31301019]
[44]
Brunden, K.R.; Trojanowski, J.Q.; Lee, V.M.Y. Advances in tau-focused drug discovery for Alzheimer’s disease and related tauopathies. Nat. Rev. Drug Discov., 2009, 8(10), 783-793.
[http://dx.doi.org/10.1038/nrd2959] [PMID: 19794442]
[45]
Sengupta, A.; Kabat, J.; Novak, M.; Wu, Q.; Grundke-Iqbal, I.; Iqbal, K. Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. Arch. Biochem. Biophys., 1998, 357(2), 299-309.
[http://dx.doi.org/10.1006/abbi.1998.0813] [PMID: 9735171]
[46]
Hanger, D.P.; Hughes, K.; Woodgett, J.R.; Brion, J.P.; Anderton, B.H. Glycogen synthase ki-nase-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(1), 58-62.
[http://dx.doi.org/10.1016/0304-3940(92)90774-2] [PMID: 1336152]
[47]
Tolosa, E.; Litvan, I.; Höglinger, G.U.; Burn, D.; Lees, A.; Andrés, M.V.; Gómez-Carrillo, B.; León, T.; Del Ser, T. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear pal-sy. Mov. Disord., 2014, 29(4), 470-478.
[http://dx.doi.org/10.1002/mds.25824] [PMID: 24532007]
[48]
Serenó, L.; Coma, M.; Rodríguez, M.; Sánchez-Ferrer, P.; Sánchez, M.B.; Gich, I.; Agulló, J.M.; Pérez, M.; Avila, J.; Guardia-Laguarta, C.; Clarimón, J.; Lleó, A.; Gómez-Isla, T. A novel GSK-3beta inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol. Dis., 2009, 35(3), 359-367.
[http://dx.doi.org/10.1016/j.nbd.2009.05.025] [PMID: 19523516]
[49]
Koehler, D.; Shah, Z.A.; Williams, F.E. The GSK3β inhibitor, TDZD-8, rescues cognition in a zebrafish model of okadaic acid-induced Alzheimer’s disease. Neurochem. Int., 2019, 122, 31-37.
[http://dx.doi.org/10.1016/j.neuint.2018.10.022] [PMID: 30392874]
[50]
Martinez, A.; Alonso, M.; Castro, A.; Pérez, C.; Moreno, F.J. First non-ATP competitive glyco-gen synthase kinase 3 beta (GSK-3beta) inhibitors: Thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer’s disease. J. Med. Chem., 2002, 45(6), 1292-1299.
[http://dx.doi.org/10.1021/jm011020u] [PMID: 11881998]
[51]
Rosa, A.O.; Egea, J.; Martínez, A.; García, A.G.; López, M.G. Neuroprotective effect of the new thiadiazolidinone NP00111 against oxygen-glucose deprivation in rat hippocampal slices: implication of ERK1/2 and PPARgamma receptors. Exp. Neurol., 2008, 212(1), 93-99.
[http://dx.doi.org/10.1016/j.expneurol.2008.03.008] [PMID: 18471812]
[52]
Lipina, T.V.; Kaidanovich-Beilin, O.; Patel, S.; Wang, M.; Clapcote, S.J.; Liu, F.; Woodgett, J.R.; Roder, J.C. Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3. Synapse, 2011, 65(3), 234-248.
[http://dx.doi.org/10.1002/syn.20839] [PMID: 20687111]
[53]
Beaulieu, J.M.; Sotnikova, T.D.; Yao, W.D.; Kockeritz, L.; Woodgett, J.R.; Gainetdinov, R.R.; Caron, M.G. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen syn-thase kinase 3 signaling cascade. Proc. Natl. Acad. Sci. USA, 2004, 101(14), 5099-5104.
[http://dx.doi.org/10.1073/pnas.0307921101] [PMID: 15044694]
[54]
Ribé, E.M.; Pérez, M.; Puig, B.; Gich, I.; Lim, F.; Cuadrado, M.; Sesma, T.; Catena, S.; Sánchez, B.; Nieto, M.; Gómez-Ramos, P.; Morán, M.A.; Cabodevilla, F.; Samaranch, L.; Ortiz, L.; Pérez, A.; Ferrer, I.; Avila, J.; Gómez-Isla, T. Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice. Neurobiol. Dis., 2005, 20(3), 814-822.
[http://dx.doi.org/10.1016/j.nbd.2005.05.027] [PMID: 16125396]
[55]
Dey, A.; Hao, S.; Wosiski-Kuhn, M.; Stranahan, A.M. Glucocorticoid-mediated activation of GSK3β promotes tau phosphorylation and impairs memory in type 2 diabetes. Neurobiol. Aging, 2017, 57, 75-83.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.05.010] [PMID: 28609678]
[56]
McCubrey, J.A.; Davis, N.M.; Abrams, S.L.; Montalto, G.; Cervello, M.; Basecke, J.; Libra, M.; Nicoletti, F.; Cocco, L.; Martelli, A.M.; Steelman, L.S. Diverse roles of GSK-3: tumor promoter-tumor suppressor, target in cancer therapy. Adv. Biol. Regul., 2014, 54(1), 176-196.
[http://dx.doi.org/10.1016/j.jbior.2013.09.013] [PMID: 24169510]
[57]
Dickey, A.; Schleicher, S.; Leahy, K.; Hu, R.; Hallahan, D.; Thotala, D.K. GSK-3β inhibition promotes cell death, apoptosis, and in vivo tumor growth delay in neuroblastoma Neuro-2A cell line. J. Neurooncol., 2011, 104(1), 145-153.
[http://dx.doi.org/10.1007/s11060-010-0491-3] [PMID: 21161565]
[58]
Carmichael, J.; Sugars, K.L.; Bao, Y.P.; Rubinsztein, D.C. Glycogen synthase kinase-3beta inhib-itors prevent cellular polyglutamine toxicity caused by the Huntington’s disease mutation. J. Biol. Chem., 2002, 277(37), 33791-33798.
[http://dx.doi.org/10.1074/jbc.M204861200] [PMID: 12097329]
[59]
Doble, B.W.; Woodgett, J.R. Exploring pluripotency with chemical genetics. Cell Stem Cell, 2009, 4(2), 98-100.
[http://dx.doi.org/10.1016/j.stem.2009.01.005] [PMID: 19200796]
[60]
Ring, D.B.; Johnson, K.W.; Henriksen, E.J.; Nuss, J.M.; Goff, D.; Kinnick, T.R.; Ma, S.T.; Reed-er, J.W.; Samuels, I.; Slabiak, T.; Wagman, A.S.; Hammond, M.E.; Harrison, S.D. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes, 2003, 52(3), 588-595.
[http://dx.doi.org/10.2337/diabetes.52.3.588] [PMID: 12606497]
[61]
Bhat, R.; Xue, Y.; Berg, S.; Hellberg, S.; Ormö, M.; Nilsson, Y.; Radesäter, A.C.; Jerning, E.; Markgren, P.O.; Borgegård, T.; Nylöf, M.; Giménez-Cassina, A.; Hernández, F.; Lucas, J.J.; Díaz-Nido, J.; Avila, J. Structural insights and biological effects of glycogen synthase kinase 3-specific in-hibitor AR-A014418. J. Biol. Chem., 2003, 278(46), 45937-45945.
[http://dx.doi.org/10.1074/jbc.M306268200] [PMID: 12928438]
[62]
Koh, S.H.; Kim, Y.; Kim, H.Y.; Hwang, S.; Lee, C.H.; Kim, S.H. Inhibition of glycogen syn-thase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS. Exp. Neurol., 2007, 205(2), 336-346.
[http://dx.doi.org/10.1016/j.expneurol.2007.03.004] [PMID: 17433298]
[63]
Bretteville, A.; Marcouiller, F.; Julien, C.; El Khoury, N.B.; Petry, F.R.; Poitras, I.; Mouginot, D.; Lévesque, G.; Hébert, S.S.; Planel, E. Hypothermia-induced hyperphosphorylation: A new model to study tau kinase inhibitors. Sci. Rep., 2012, 2(1), 480.
[http://dx.doi.org/10.1038/srep00480] [PMID: 22761989]
[64]
Eldar-Finkelman, H.; Martinez, A. GSK-3 inhibitors: Preclinical and clinical focus on CNS. Front. Mol. Neurosci., 2011, 4, 32.
[http://dx.doi.org/10.3389/fnmol.2011.00032] [PMID: 22065134]
[65]
Phiel, C.J.; Wilson, C.A.; Lee, V.M.; Klein, P.S. GSK-3alpha regulates production of Alz-heimer’s disease amyloid-beta peptides. Nature, 2003, 423(6938), 435-439.
[http://dx.doi.org/10.1038/nature01640] [PMID: 12761548]
[66]
Prajapat, M.; Sarma, P.; Shekhar, N.; Kaur, H.; Singh, S.; Kumar, S.; Kaur, H.; Mahendiratta, S.; Sharma, A.R.; Kaur, S.; Mahalmani, V.M.; Medhi, B. In silico docking and comparative ADMET pro-file of different glycogen synthase kinase 3 beta inhibitors as the potential leads for the development of anti-Alzheimer drug therapy. J. Adv. Pharm. Technol. Res., 2020, 11(4), 194-201.
[http://dx.doi.org/10.4103/japtr.JAPTR_178_19] [PMID: 33425704]
[67]
Pan, J.Q.; Lewis, M.C.; Ketterman, J.K.; Clore, E.L.; Riley, M.; Richards, K.R.; Berry-Scott, E.; Liu, X.; Wagner, F.F.; Holson, E.B.; Neve, R.L.; Biechele, T.L.; Moon, R.T.; Scolnick, E.M.; Petryshen, T.L.; Haggarty, S.J. AKT kinase activity is required for lithium to modulate mood-related behaviors in mice. Neuropsychopharmacology, 2011, 36(7), 1397-1411.
[http://dx.doi.org/10.1038/npp.2011.24] [PMID: 21389981]
[68]
Yang, Y.; Wang, Q.Q.; Bozinov, O.; Xu, R.X.; Sun, Y.L.; Wang, S.S. GSK-3 inhibitor CHIR99021 enriches glioma stem-like cells. Oncol. Rep., 2020, 43(5), 1479-1490.
[http://dx.doi.org/10.3892/or.2020.7525] [PMID: 32323804]
[69]
Kobayashi, H.; Nishimura, H.; Kudo, N.; Osada, H.; Yoshida, M. A novel GSK3 inhibitor that promotes self-renewal in mouse embryonic stem cells. Biosci. Biotechnol. Biochem., 2020, 84(10), 2113-2120.
[http://dx.doi.org/10.1080/09168451.2020.1789445] [PMID: 32640867]
[70]
Kurgan, N.; Whitley, K.C.; Maddalena, L.A.; Moradi, F.; Stoikos, J.; Hamstra, S.I.; Rubie, E.A.; Kumar, M.; Roy, B.D.; Woodgett, J.R.; Stuart, J.A.; Fajardo, V.A. A low-therapeutic dose of lithium inhibits GSK3 and enhances myoblast fusion in C2C12 cells. Cells, 2019, 8(11), 1340-1349.
[http://dx.doi.org/10.3390/cells8111340] [PMID: 31671858]
[71]
Govarthanan, K.; Vidyasekar, P.; Gupta, P.K.; Lenka, N.; Verma, R.S. Glycogen synthase kinase 3β inhibitor- CHIR 99021 augments the differentiation potential of mesenchymal stem cells. Cytotherapy, 2020, 22(2), 91-105.
[http://dx.doi.org/10.1016/j.jcyt.2019.12.007] [PMID: 31980369]
[72]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[73]
Gandini, A.; Bartolini, M.; Tedesco, D.; Martinez-Gonzalez, L.; Roca, C.; Campillo, N.E.; Zaldi-var-Diez, J.; Perez, C.; Zuccheri, G.; Miti, A.; Feoli, A.; Castellano, S.; Petralla, S.; Monti, B.; Rossi, M.; Moda, F.; Legname, G.; Martinez, A.; Bolognesi, M.L. Tau-centric multitarget approach for alz-heimer’s disease: development of first-in-class dual glycogen synthase kinase 3 β and tau-aggregation inhibitors. J. Med. Chem., 2018, 61(17), 7640-7656.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00610] [PMID: 30078314]
[74]
Stanciu, G.D.; Luca, A.; Rusu, R.N.; Bild, V.; Beschea Chiriac, S.I.; Solcan, C.; Bild, W.; Aba-bei, D.C. Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules, 2019, 10(1), 40-47.
[http://dx.doi.org/10.3390/biom10010040] [PMID: 31888102]
[75]
Wang, W.; Li, M.; Wang, Y.; Li, Q.; Deng, G.; Wan, J.; Yang, Q.; Chen, Q.; Wang, J. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats. Mol. Neurobiol., 2016, 53(10), 7028-7036.
[http://dx.doi.org/10.1007/s12035-015-9607-2] [PMID: 26671619]
[76]
De Simone, A.; Tumiatti, V.; Andrisano, V.; Milelli, A. Glycogen synthase kinase 3β: a new gold rush in anti-Alzheimer’s disease multitarget drug discovery? J. Med. Chem., 2021, 64(1), 26-41.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00931] [PMID: 33346659]

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