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SPECIAL FOCUS: Alzheimer's Disease Therapy - Review

Further understanding of tau phosphorylation: implications for therapy

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References

  • Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci USA 1975;72(5):1858-62
  • Drubin DG, Kirschner MW. Tau protein function in living cells. J Cell Biol 1986;103(6 Pt 2):2739-46
  • Terwel D, Dewachter I, Van Leuven F. Axonal transport, tau protein, and neurodegeneration in Alzheimer’s disease. Neuromolecular Med 2002;2(2):151-65
  • Neve RL, Harris P, Kosik KS, et al. Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Brain Res 1986;387(3):271-80
  • Andreadis A. Tau splicing and the intricacies of dementia. J Cell Physiol 2012;227(3):1220-5
  • Serrano L, de la Torre J, Maccioni RB, Avila J. Involvement of the carboxyl-terminal domain of tubulin in the regulation of its assembly. Proc Natl Acad Sci USA 1984;81(19):5989-93
  • Lee G, Neve RL, Kosik KS. The microtubule binding domain of tau protein. Neuron 1989;2(6):1615-24
  • Avila J, Pérez M, Lim F, et al. Tau in neurodegenerative diseases: tau phosphorylation and assembly. Neurotox Res 2004;6(6):477-82
  • Goedert M, Spillantini MG, Potier MC, et al. Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J 1989;8(2):393-9
  • Grundke-Iqbal I, Iqbal K, Quinlan M, et al. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 1986;261(13):6084-9
  • Grundke-Iqbal I, Iqbal K, Tung YC, et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986;83(13):4913-17
  • Kosik KS, Joachim CL, Selkoe DJ. Microtubule-associated protein tau is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci USA 1986;83(11):4044-8
  • Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 1992;42(3):631-9
  • Spillantini MG, Goedert M. Tau protein pathology in neurodegenerative diseases. Trends Neurosci 1998;21(10):428-33
  • Mandell JW, Banker GA. A spatial gradient of tau protein phosphorylation in nascent axons. J Neurosci 1996;16(18):5727-40
  • Ebneth A, Godemann R, Stamer K, et al. Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease. J Cell Biol 1998;143(3):777-94
  • Dixit R, Ross JL, Goldman YE, Holzbaur EL. Differential regulation of dynein and kinesin motor proteins by tau. Science 2008;319(5866):1086-9
  • Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron 2011;70(3):410-26
  • Brandt R, Leger J, Lee G. Interaction of tau with the neural plasma membrane mediated by tau’s amino-terminal projection domain. J Cell Biol 1995;131:1327-40
  • Noble W, Hanger DP, Miller CC, Lovestone S. The importance of tau phosphorylation for neurodegenerative diseases. Front Neurol 2013;4:83
  • Pooler AM, Hanger DP. Functional implications of the association of tau with the plasma membrane. Biochem Soc Trans 2010;38(4):1012-15
  • Kampers T, Friedhoff P, Biernat J, et al. RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments. FEBS Lett 1996;399(3):344-9
  • Krylova SM, Musheev M, Nutiu R, et al. Tau protein binds single-stranded DNA sequence specifically–the proof obtained in vitro with non-equilibrium capillary electrophoresis of equilibrium mixtures. FEBS Lett 2005;579(6):1371-5
  • Sultan A, Nesslany F, Violet M, et al. Nuclear tau, a key player in neuronal DNA protection. J Biol Chem 2011;286(6):4566-75
  • Medina M, Avila J. Is tau a prion-like protein? J Alzheimers Dis 2014;40(Suppl 1):S1-3
  • Medina M, Avila J. New perspectives on the role of tau in Alzheimer´s disease. Implications for therapy. Biochem Pharmacol 2014;88:540-7
  • Dawson HN, Ferreira A, Eyster MV, et al. Inhibition of neuronal maturation in primary hippocampal neurons from tau-deficient mice. J Cell Sci 2001;114:1179-87
  • Merino-Serrais P, Benavides-Piccione R, Blazquez-Llorca L, et al. The influence of phospho-τ on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease. Brain 2013;136(6):1913-28
  • Spillantini MG, Goedert M. Tau pathology and neurodegeneration. Lancet Neurol 2013;12(6):609-22
  • Simón-Sánchez J, Schulte C, Bras JM, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet 2009;41(12):1308-12
  • Edwards TL, Scott WK, Almonte C, et al. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann Hum Genet 2010;74:97-109
  • Jaworski T, Kügler S, Van Leuven F. Modelling of tau-mediated synaptic and neuronal degeneration in Alzheimer’s disease. Int J Alzheimers Dis 2010;2010:10, 10.4061/2010/573138
  • Ledesma MD, Medina M, Avila J. The in vitro formation of recombinant tau polymers: effect of phosphorylation and glycation. Mol Chem Neuropathol 1996;27(3):249-58
  • Avila J. Tau aggregation into fibrillar polymers: taupathies. FEBS Lett 2000;476(1-2):89-92
  • Alonso AC, Grundke-Iqbal I, Iqbal K. Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 1996;2(7):783-7
  • Avila J. The tau code. Front Aging Neurosci 2009;1:1
  • Buée L, Bussière T, Buée-Scherrer V, et al. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 2000;33(1):95-130
  • Hernandez F, Ávila J. Tauopathies. Cell Mol Life Sci 2009;64(17):2219-33
  • Alonso AD, Zaidi T, Novak M, et al. Interaction of tau isoforms with Alzheimer’s disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein. J Biol Chem 2001;276(41):37967-73
  • Wang JZ, Grundke-Iqbal I, Iqbal K. Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur J Neurosci 2007;25(1):59-68
  • Hanger DP, Anderton BH, Noble W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 2009;15(3):112-19
  • Wang JZ, Xia YY, Grundke-Iqbal I, Iqbal K. Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J Alzheimers Dis 2013;33(Suppl 1):S123-39
  • Zhang X, Hernandez I, Rei D, et al. Diaminothiazoles modify Tau phosphorylation and improve the tauopathy in mouse models. J Biol Chem 2013;288(30):22042-56
  • Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 2008;5(3):443-57
  • Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer’s disease. J Neurochem 2008;104(6):1433-9
  • Medina M, Castro A. Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic. Curr Opin Drug Discov Devel 2008;11(4):533-43
  • Medina M. Recent developments in tau-based therapeutics for neurodegenerative diseases. Recent Pat CNS Drug Discov 2011;6(1):20-30
  • Forlenza OV, Diniz BS, Radanovic M, et al. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 2011;198(5):351-6
  • Domínguez JM, Fuertes A, Orozco L, et al. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem 2012;287(2):893-904
  • del Ser T, Steinwachs KC, Gertz HJ, et al. Treatment of Alzheimer’s disease with the GSK-3 inhibitor tideglusib: a pilot study. J Alzheimers Dis 2013;33(1):205-15
  • Höglinger GU, Huppertz HJ, Wagenpfeil S, et al. Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial. Mov Disord 2014;29(4):479-87
  • Tolosa E, Litvan I, Höglinger GU, et al. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord 2014;29(4):470-8
  • Lovestone S, Boada M, Dubois B, et al. A phase II study of tideglusib in Alzheimer’s disease. J Alzheimers Dis 2014; In press
  • Gong CX, Iqbal K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem 2008;15(23):2321-8
  • Gong CX, Singh TJ, Grundke-Iqbal I, Iqbal K. Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem 1993;61:921-7
  • Chen S, Li B, Grundke-Iqbal I, Iqbal K. I1PP2A affects tau phosphorylation via association with the catalytic subunit of protein phosphatase 2A. J Biol Chem 2008;283(16):10513-21
  • Wang X, Blanchard J, Kohlbrenner E, et al. The carboxy-terminal fragment of inhibitor-2 of protein phosphatase-2A induces Alzheimer disease pathology and cognitive impairment. FASEB J 2010;24(11):4420-321
  • Landrieu I, Smet-Nocca C, Amniai L, et al. Molecular implication of PP2A and Pin1 in the Alzheimer’s disease specific hyperphosphorylation of Tau. PLoS One 2011;6(6):e21521
  • Sontag JM, Nunbhakdi-Craig V, Mitterhuber M, et al. Regulation of protein phosphatase 2A methylation by LCMT1 and PME-1 plays a critical role in differentiation of neuroblastoma cells. J Neurochem 2010;115(6):1455-65
  • Sontag JM, Nunbhakdi-Craig V, Sontag E. Leucine carboxyl methyltransferase 1 (LCMT1)-dependent methylation regulates the association of protein phosphatase 2A and Tau protein with plasma membrane microdomains in neuroblastoma cells. J Biol Chem 2013;288(38):27396-405
  • Iqbal K, Wang X, Blanchard J, et al. Alzheimer’s disease neurofibrillary degeneration: pivotal and multifactorial. Biochem Soc Trans 2010;38(4):962-6
  • de Calignon A, Spires-Jones TL, Pitstick R, et al. Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy. J Neuropathol Exp Neurol 2009;68(7):757-61
  • Medina M, Avila J. The role of extracellular Tau in the spreading of neurofibrillary pathology. Front Cell Neurosci 2014;8:113
  • Chai X, Dage JL, Citron M. Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol Dis 2012;48(3):356-66
  • Saman S, Kim W, Raya M, et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem 2012;287:3842-9
  • Simón D, García-García E, Gómez-Ramos A, et al. Tau overexpression results in its secretion via membrane vesicles. Neurodegener Dis 2012;10(1-4):73-5
  • Simón D, García-García E, Royo F, et al. Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Lett 2012;586(1):47-54
  • Yamada K, Cirrito JR, Stewart FR, et al. In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J Neurosci 2011;31(37):13110-17
  • Marklund N, Blennow K, Zetterberg H, et al. Monitoring of brain interstitial total tau and beta amyloid proteins by microdialysis in patients with traumatic brain injury. J Neurosurg 2009;110(6):1227-37
  • Magnoni S, Esparza TJ, Conte V, et al. Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury. Brain 2012;135(4):1268-80
  • Pooler AM, Phillips EC, Lau DH, et al. Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 2013;14(4):389-94
  • Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 2010;6(2):108-19
  • Rosenmann H, Grigoriadis N, Karussis D, et al. Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Arch Neurol 2006;63(10):1459-67
  • Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci 2007;27(34):9115-29
  • Boutajangout A, Quartermain D, Sigurdsson EM. Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 2010;30(49):16559-66
  • Theunis C, Crespo-Biel N, Gafner V, et al. Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau.P301L mice that model tauopathy. PLoS One 2013;8(8):e72301
  • Boimel M, Grigoriadis N, Lourbopoulos A, et al. Efficacy safety of immunization with phosphorylated tau against neurofibrillary and tangles in mice. Exp Neurol 2010;224(2):472-85
  • Troquier L, Caillierez R, Burnouf S, et al. Targeting phospho-Ser422 by active Tau Immunotherapy in the THYTau22 mouse model: a suitable therapeutic approach. Curr Alzheimer Res 2012;9(4):397-405
  • Boutajangout A, Ingadottir J, Davies P, Sigurdsson EM. Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J Neurochem 2011;118(4):658-67
  • Kontsekova E, Ivanovova N, Handzusova M, Novak M. Chaperone-like antibodies in neurodegenerative tauopathies: implication for immunotherapy. Cell Mol Neurobiol 2009;29:793-8
  • Zilka N, Kontsekova E, Novak M. Chaperone-like antibodies targeting misfolded tau protein: new vistas in the immunotherapy of neurodegenerative foldopathies. J Alzheimers Dis 2008;15:169-79
  • Orgogozo JM, Gilman S, Dartigues JF, et al. Subcaute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003;61(1):46-54
  • Gilman S, Koller M, Black RS, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005;64(9):1553-62
  • Rozenstein-Tsalkovich L, Grigoriadis N, Lourbopoulos A, et al. Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation. Exp Neurol 2013;248:451-6
  • Yoshiyama Y, Higuchi M, Zhang B, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007;53(3):337-51
  • Frost B, Jacks RL, Diamond MI. Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 2009;284(19):12845-52
  • Clavaguera F, Bolmont T, Crowther RA, et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 2009;11(7):909-13
  • Medina M, Avila J. Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer’s disease. Curr Pharm Des 2010;16(25):2790-8
  • Medina M, Wandosell F. Deconstructing GSK-3: the fine regulation of its activity. Int J Alzheimers Dis 2011;2011:479249
  • Medina M, Avila J. New insights into the role of glycogen synthase kinase-3 in Alzheimer’s disease. Expert Opin Ther Targets 2014;18(1):69-77

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