Further understanding of tau phosphorylation: Implications for therapy

Expert Review of Neurotherapeutics

Volumn 15, Issue 1, 2014, Pages 115-122

  Medina, Miguel ^a,b   Avila, Jesus ^a,c  

^a CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED SOBRE ENFERMEDADES NEURODEGENERATIVAS CIBERNED   (Spain)

^b Instituto de Salud Carlos III   (Spain)

^c CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOA   (Spain)

Author keywords

Aggregation; Alzheimer; dementia; kinases; memory; neurodegeneration; neurofibrillary tangles; phosphorylation; tau; tauopathies

Indexed keywords

TAU PROTEIN; NEUROLEPTIC AGENT;

ALZHEIMER DISEASE; CELL FUNCTION; CELL STRUCTURE; HUMAN; MICROTUBULE; NEUROFILAMENT; NONHUMAN; PATHOGENESIS; PHYSIOLOGICAL PROCESS; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; REVIEW; TAUOPATHY; DRUG EFFECTS; METABOLISM; PHOSPHORYLATION; TAUOPATHIES;

ANTIPSYCHOTIC AGENTS; HUMANS; PHOSPHORYLATION; TAU PROTEINS; TAUOPATHIES;

EID: 84920765954     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/14737175.2015.1000864     Document Type: Review

References (90)

1. 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
2. Drubin DG, Kirschner MW. Tau protein function in living cells. J Cell Biol 1986; 103(6 Pt 2):2739-46
3. Terwel D, Dewachter I, Van Leuven F. Axonal transport, tau protein, and neurodegeneration in Alzheimer's disease. Neuromolecular Med 2002;2(2):151-65
4. 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.Brain Res 1986;387(3):271-80
5. Andreadis A. Tau splicing and the intricacies of dementia. J Cell Physiol 2012; 227(3):1220-5
6. 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
7. Lee G, Neve RL, Kosik KS. The microtubule binding domain of tau protein. Neuron 1989;2(6):1615-24
8. Avila J, Perez M, Lim F, et al. Tau in neurodegenerative diseases: tau phosphorylation and assembly. Neurotox Res 2004;6(6):477-82
9. 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
10. 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
11. 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
12. 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
13. 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
14. Spillantini MG, Goedert M. Tau protein pathology in neurodegenerative diseases. Trends Neurosci 1998;21(10):428-33
15. Mandell JW, Banker GA. A spatial gradient of tau protein phosphorylation in nascent axons. J Neurosci 1996;16(18):5727-40
16. 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
17. Dixit R, Ross JL, Goldman YE, Holzbaur EL. Differential regulation of dynein and kinesin motor proteins by tau. Science 2008;319(5866):1086-9
18. Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron 2011;70(3): 410-26
19. 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
20. Noble W, Hanger DP, Miller CC, Lovestone S. The importance of tau phosphorylation for neurodegenerative diseases. Front Neurol 2013;4:83
21. Pooler AM, Hanger DP. Functional implications of the association of tau with the plasma membrane. Biochem Soc Trans 2010;38(4):1012-15
22. 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
23. 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
24. 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
25. Medina M, Avila J. Is tau a prion-like protein J Alzheimers Dis 2014;40(Suppl 1):S1-3
26. Medina M, Avila J. New perspectives on the role of tau in Alzheimeŕs disease. Implications for therapy. Biochem Pharmacol 2014;88:540-7
27. 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
28. Merino-Serrais P, Benavides-Piccione R, Blazquez-Llorca L, et al. The influence of phospho-t on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease. Brain 2013;136(6): 1913-28
29. Spillantini MG, Goedert M. Tau pathology and neurodegeneration. Lancet Neurol 2013;12(6):609-22
30. Simon-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
31. 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
32. 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, doi:10.4061/2010/573138
33. 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
34. Avila J. Tau aggregation into fibrillar polymers: taupathies. FEBS Lett 2000; 476(1-2):89-92
35. 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
36. Avila J. The tau code. Front Aging Neurosci 2009;1:1
37. Buee L, Bussière T, Buee-Scherrer V, et al. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 2000;33(1):95-130
38. Hernandez F, Á vila J. Tauopathies. Cell Mol Life Sci 2009;64(17):2219-33
39. 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
40. 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
41. Hanger DP, Anderton BH, Noble W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 2009;15(3):112-19
42. 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
43. 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
44. Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 2008;5(3): 443-57
45. Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer's disease. J Neurochem 2008;104(6):1433-9
46. Medina M, Castro A. Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic. Curr Opin Drug Discov Devel 2008;11(4): 533-43
47. Medina M. Recent developments in tau-based therapeutics for neurodegenerative diseases. Recent Pat CNS Drug Discov 2011;6(1):20-30
48. 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
49. Domńguez JM, Fuertes A, Orozco L, et al. Evidence for irreversible inhibition of glycogen synthase kinase-3b by tideglusib. J Biol Chem 2012;287(2):893-904
50. 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
51. 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
52. 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
53. Lovestone S, Boada M, Dubois B, et al. A phase II study of tideglusib in Alzheimer's disease. J Alzheimers Dis 2014; In press
54. 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
55. Gong CX, Singh TJ, Grundke-Iqbal I, Iqbal K. Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem 1993;61:921-7
56. 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
57. 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
58. 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
59. 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
60. 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
61. Iqbal K, Wang X, Blanchard J, et al. Alzheimer's disease neurofibrillary degeneration: pivotal and multifactorial. Biochem Soc Trans 2010;38(4):962-6
62. 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
63. Medina M, Avila J. The role of extracellular Tau in the spreading of neurofibrillary pathology. Front Cell Neurosci 2014;8:113
64. Chai X, Dage JL, Citron M. Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol Dis 2012;48(3):356-66
65. 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
66. Simon D, Garcá-Garcá E, Gomez-Ramos A, et al. Tau overexpression results in its secretion via membrane vesicles. Neurodegener Dis 2012;10(1-4): 73-5
67. Simo-n D, Garcá-Garcá E, Royo F, et al. Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Lett 2012;586(1):47-54
68. 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
69. 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
70. Magnoni S, Esparza TJ, Conte V, et al. Tau elevations in the brain extracellular space correlate with reduced amyloid-b levels and predict adverse clinical outcomes after severe traumatic brain injury. Brain 2012;135(4): 1268-80
71. 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
72. Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy Nat Rev Neurol 2010; 6(2):108-19
73. 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
74. 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
75. 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
76. 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
77. 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
78. 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
79. 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
80. Kontsekova E, Ivanovova N, Handzusova M, Novak M. Chaperone-like antibodies in neurodegenerative tauopathies: implication for immunotherapy. Cell Mol Neurobiol 2009;29:793-8
81. 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
82. 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
83. 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
84. 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
85. 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
86. 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
87. 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
88. 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
89. Medina M, Wandosell F. Deconstructing GSK-3: the fine regulation of its activity. Int J Alzheimers Dis 2011;2011:479249
90. 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