Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimers disease

Free Radical Biology and Medicine

Volumn 83, Issue , 2015, Pages 186-191

  Lloret, A ^a   Fuchsberger, T ^a   Giraldo, E ^a   Vina J ^a  

^a UNIVERSITY OF VALENCIA   (Spain)

Author keywords

Alzheimers disease; Amyloid ; Dementia p Tau; Free radicals; Neurodegeneration

Indexed keywords

AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; CYCLIN DEPENDENT KINASE 5; GLYCOGEN SYNTHASE KINASE 3BETA; MITOGEN ACTIVATED PROTEIN KINASE P38; PEPTIDYLPROLYL ISOMERASE PIN1; REACTIVE OXYGEN METABOLITE; REGULATOR OF CALCINEURIN 1; REGULATOR PROTEIN; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ENZYME ACTIVATION; HUMAN; MITOCHONDRION; MOLECULAR PATHOLOGY; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; CHEMISTRY; METABOLISM; PATHOLOGY; PHOSPHORYLATION; PROTEIN AGGREGATION, PATHOLOGICAL;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; HUMANS; PHOSPHORYLATION; PROTEIN AGGREGATION, PATHOLOGICAL; TAU PROTEINS;

EID: 84927602807     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2015.02.028     Document Type: Review

References (90)

1. A. Alzheimer Über eine eigenartige Erkrankung der Hirnrinde Allg. Z. Psychiatr. 64 1907 146 148
2. C.G. Glabe Structural classification of toxic amyloid oligomers J. Biol. Chem. 283 2008 29639 29643
3. P.N. Lacor, M.C. Buniel, L. Chang, S.J. Fernandez, Y. Gong, K.L. Viola, M.P. Lambert, P.T. Velasco, E.H. Bigio, C.E. Finch, G.A. Krafft, and W.L. Klein Synaptic targeting by Alzheimers-related amyloid β oligomers J. Neurosci. 24 2004 10191 10200
4. L.M. Billings, S. Oddo, K.N. Green, J.L. McGaugh, and F.M. LaFerla Intraneuronal Aβ causes the onset of early Alzheimers disease-related cognitive deficits in transgenic mice Neuron 45 2005 675 688
5. S. Lesne, M.T. Koh, L. Kotilinek, R. Kayed, C.G. Glabe, A. Yang, M. Gallagher, and K.H. Ashe A specific amyloid-β protein assembly in the brain impairs memory Nature 440 2006 352 357
6. C.A. McLean, R.A. Cherny, F.W. Fraser, S.J. Fuller, M.J. Smith, K. Beyreuther, A.I. Bush, and C.L. Masters Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimers disease Ann. Neurol. 46 1999 860 866
7. J. Naslund, V. Haroutunian, R. Mohs, K.L. Davis, P. Davies, P. Greengard, and J.D. Buxbaum Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline JAMA 283 2000 1571 1577
8. A. Deshpande, E. Mina, C. Glabe, and J. Busciglio Different conformations of amyloid β induce neurotoxicity by distinct mechanisms in human cortical neurons J. Neurosci. 26 2006 6011 6018
9. H. Zempel, E. Thies, E. Mandelkow, and E.M. Mandelkow Aβ oligomers cause localized Ca2+ elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines J. Neurosci. 30 2010 11938 11950
10. A. Lloret, M.C. Badia, E. Giraldo, G. Ermak, M.D. Alonso, F.V. Pallardó, K.J. Davies, and J. Viña Amyloid-β toxicity and Tau hyperphosphorylation are linked via RCAN1 in Alzheimers disease J. Alzheimers Dis. 27 2011 701 709
11. S. Johansson, A. Jämsä, M. Vasänge, B. Winblad, J. Luthman, and R.F. Cowburn Increased Tau phosphorylation at the Ser396 epitope after amyloid β-exposure in organotypic cultures Neuroreport 17 2006 907 911
12. M.A. Chabrier, M. Blurton-Jones, A.A. Agazaryan, J.L. Nerhus, H. Martinez-Coria, and F.M. LaFerla Soluble Aβ promotes wild-type Tau pathology in vivo J. Neurosci. 32 2012 17345 17350
13. S.H. Choi, Y.H. Kim, M. Hebisch, C. Sliwinski, S. Lee, C. DAvanzo, H. Chen, B. Hooli, C. Asselin, J. Muffat, K.L. Klee, C. Zhang, B.J. Wainger, M. Peitz, D.M. Kovacs, C.J. Woolf, S.L. Wagner, R.E. Tanzi, and D.Y. Kim A three-dimensional human neural cell culture model of Alzheimers disease Nature 515 2014 274 278
14. H.K. Anandatheerthavarada, G. Biswas, M.A. Robin, and N.G. Avadhani Mitochondrial targeting and a novel transmembrane arrest of Alzheimers amyloid precursor protein impairs mitochondrial function in neuronal cells J. Cell Biol. 161 2003 41 54
15. L. Devi, B.M. Prabhu, D.F. Galati, N.G. Avadhani, and H.K. Anandatheerthavarada Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimers disease brain is associated with mitochondrial dysfunction J. Neurosci. 26 2006 9057 9068
16. S.M. Cardoso, I. Santana, R.H. Swedlow, and C.R. Oliveira Mitochondria dysfunction of Alzheimers disease cybrids enhances Aβ toxicity J. Neurochem. 89 2004 1417 1426
17. W.D. Parker Jr, and J.K. Parks Cytochrome c oxidase in Alzheimers disease brain: purification and characterization Neurology 45 1995 482 486
18. V. Rhein, X. Song, A. Wiesner, L.M. Ittner, G. Baysang, F. Meier, L. Ozmen, H. Bluethmann, S. Dröse, U. Brandt, E. Savaskan, C. Czech, J. Götz, and A. Eckert Amyloid-β and Tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimers disease mice Proc. Natl. Acad. Sci. USA 106 2009 20057 20062
19. A. Lloret, M.C. Badía, N.J. Mora, A. Ortega, F.V. Pallardó, M.D. Alonso, and J. Viña Gender and age-dependent differences in the mitochondrial apoptogenic pathway in Alzheimers disease Free Radic. Biol. Med. 44 2008 2019 2025
20. R. Sultana, and D.A. Butterfield Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment J. Bioenerg. Biomembr. 41 2009 441 446
21. D.A. Butterfield, F. Di Domenico, A.M. Swomley, E. Head, and M. Perluigi Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: overlaps in Down syndrome and Alzheimers disease brain Biochem. J. 463 2014 177 189
22. D.A. Butterfield Β amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimers disease Chem. Res. Toxicol. 10 1997 495 506
23. D.A. Butterfield, J. Drake, C. Pocernich, and A. Castegna Evidence of oxidative damage in Alzheimers disease brain: central role for amyloid β peptide Trends Mol. Med. 7 2001 548 554
24. D.A. Butterfield The 2013 SFRBM discovery award: selected discoveries from the Butterfield laboratory of oxidative stress and its sequela in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment Free Radic. Biol. Med. 74 2014 157 174
25. C.M. Lauderback, J.M. Hackett, F.F. Huang, J.N. Keller, L.I. Szweda, W.R. Markesbery, and D.A. Butterfield The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimers disease brain: the role of Aβ1-42 J. Neurochem. 78 2001 413 416
26. C. Merkwirth, P. Martinelli, A. Korwitz, M. Morbin, H.S. Brönneke, S.D. Jordan, E.I. Rugarli, and T. Langer Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to Tau hyperphosphorylation and neurodegeneration PLoS Genet. 8 2012 e1003021
27. M. Llorens-Martín, G. López-Doménech, E. Soriano, and J. Avila GSK3β is involved in the relief of mitochondria pausing in a Tau-dependent manner PLoS One 6 2011 e27686
28. S. Melov, P.A. Adlard, K. Morten, F. Johnson, T.R. Golden, D. Hinerfeld, B. Schilling, C. Mavros, C.L. Masters, I. Volitakis, Q.X. Li, K. Laughton, A. Hubbard, R.A. Cherny, B. Gibson, and A.I. Bush Mitochondrial oxidative stress causes hyperphosphorylation of Tau PLoS One 2 2007 e536
29. J.J. Fuentes, M.A. Pritchard, A.M. Planas, A. Bosch, I. Ferrer, and X. Estivill A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart Hum. Mol. Genet 4 1995 1935 1944
30. D.R. Crawford, C. Edbauer-Nechamen, G.P. Schools, S.L. Salmon, J.M.S. Davies, and K.J.A. Davies Oxidant-modulated gene expression K.J.A. Davies, F. Ursini, The Oxygen Paradox 1995 CLEUP University Press Padova 327 335
31. D.R. Crawford, K.P. Leahy, N. Abramova, L. Lan, Y. Wang, and K.J. Davies Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress Arch. Biochem. Biophys. 342 1997 6 12
32. B. Rothermel, R.B. Vega, J. Yang, H. Wu, R. Bassel-Duby, and R.S. Williams A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling J. Biol. Chem. 275 2000 8719 8725
33. K.J.A. Davies, G. Ermak, B.A. Rothermel, M. Pritchard, J. Heitman, J. Ahnn, F. Henrique-Silva, D. Crawford, S. Canaider, P. Strippoli, P. Carinci, K.T. Min, D.S. Fox, K.W. Cunningham, R. Bassel-Duby, E.N. Olson, Z. Zhang, R.S. Williams, H.P. Gerber, M. Pérez-Riba, H. Seo, X. Cao, C.B. Klee, J.M. Redondo, L.J. Maltais, E.A. Bruford, S. Povey, J.D. Molkentin, F.D. McKeon, E.J. Duh, G.R. Crabtree, M.S. Cyert, S. de la Luna, and X. Estivill Renaming the DSCR1/Adapt78 gene family as RCAN: regulators of calcineurin FASEB J 21 2007 3023 3028
34. A.N. Mitchell, L. Jayakumar, I. Koleilat, J. Qian, C. Sheehan, D. Bhoiwala, S.F. Hushmendy, J.M. Heuring, and D.R. Crawford Brain expression of the calcineurin inhibitor RCAN1 (Adapt78) Arch. Biochem. Biophys. 467 2007 185 192
35. D.R. Crawford, K.P. Leahy, N. Abramova, L. Lan, Y. Wang, and K.J.A. Davies Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress Arch. Biochem. Biophys. 342 1997 6 12
36. G. Ermak, M.A. Pritchard, S. Dronjak, B. Niu, and K.J.A. Davies Do RCAN1 proteins link chronic stress with neurodegeneration? FASEB J 25 2011 3306 3311
37. G. Ermak, and K.J.A. Davies Chronic high levels of the RCAN1-1L protein may promote neurodegeneration and Alzheimer disease Free Radic. Biol. Med. 62 2013 47 51
38. S.G. Norman, and G.V. Johnson Compromised mitochondrial function results in dephosphorylation of Tau through a calcium-dependent process in rat brain cerebral cortical slices Neurochem. Res. 19 1994 1151 1158
39. G. Ermak, T.E. Morgan, and K.J.A. Davies Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimers disease J. Biol. Chem. 276 2001 38787 38794
40. C.D. Harris, G. Ermak, and K.J.A. Davies RCAN1-1L is overexpressed in neurons of Alzheimers disease patients FEBS J. 274 2007 1715 1724
41. G. Ermak, and K.J.A. Davies DSCR1 (Adapt78) - a Janus gene providing stress protection but causing Alzheimers disease? IUBMB Life 55 2003 29 31
42. G. Ermak, S. Sojitra, F. Yin, E. Cadenas, A.M. Cuervo, and K.J.A. Davies Chronic expression of RCAN1-1L induces mitochondrial autophagy and a metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells J. Biol. Chem. 287 2012 14088 14098
43. G. Ermak, C.D. Harris, D. Battocchio, and K.J.A. Davies RCAN1 (DSCR1 or Adapt78) stimulates expression of GSK-3β FEBS J. 273 2006 2100 2109
44. M. Townsend, T. Mehta, and D.J. Selkoe Soluble Aβ inhibits specific signal transduction cascades common to the insulin receptor pathway J. Biol. Chem. 282 2007 33305 33312
45. M. Perluigi, G. Pupo, A. Tramutola, C. Cini, R. Coccia, E. Barone, E. Head, D.A. Butterfield, and F. Di Domenico Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain Biochim. Biophys. Acta 1842 2014 1144 1153
46. H.K. Lee, P. Kumar, Q. Fu, K.M. Rosen, and H.W. Querfurth The insulin/Akt signaling pathway is targeted by intracellular β-amyloid Mol. Biol. Cell. 20 2009 1533 1544
47. P. Ly, Y. Wu, H. Zou, R. Wang, W. Zhou, A. Kinoshita, M. Zhang, Y. Yang, F. Cai, J. Woodgett, and W. Song Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes J. Clin. Invest. 123 2013 224 235
48. T. Engel, F. Hernández, J. Avila, and J.J. Lucas Full reversal of Alzheimers disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3 J. Neurosci. 26 2006 5083 5090
49. S.A. Farr, J.L. Ripley, R. Sultana, Z. Zhang, M.L. Niehoff, T.L. Platt, M.P. Murphy, J.E. Morley, V. Kumar, and D.A. Butterfield Antisense oligonucleotide against GSK-3B in brain of SAMP8 mice improves learning and memory and decreases oxidative stress: involvement of transcription factor Nrf-2 and implications for Alzheimers disease Free Radic. Biol. Med. 67 2014 387 395
50. T. Grune, D. Botzen, M. Engels, P. Voss, B. Kaiser, T. Jung, S. Grimm, G. Ermak, and K.J.A. Davies Tau protein degradation is catalyzed by the ATP/ubiquitin-independent 20S proteasome under normal cell conditions Arch. Biochem. Biophys. 500 2010 181 188
51. D. Poppek, S. Keck, G. Ermak, T. Jung, A. Stolzing, O. Ullrich, T. Grune, and K.J.A. Davies Phosphorylation mediates the turnover of the tau protein by the proteasome: influence of RCAN1 and oxidative stress Biochem. J. 400 2006 511 520
52. P.J. Lu, G. Wulf, X.Z. Zhou, P. Davies, and K.P. Lu The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated Tau protein Nature 399 1999 784 788
53. Y.C. Liou, A. Sun, A. Ryo, X.Z. Zhou, Z.X. Yu, H.K. Huang, T. Uchida, R. Bronson, G. Bing, X. Li, T. Hunter, and K.P. Lu Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration Nature 424 2003 556 561
54. R. Sultana, D. Boyd-Kimball, H.F. Poon, J. Cai, W.M. Pierce, J.B. Klein, W.R. Markesbery, X.Z. Zhou, K.P. Lu, and D.A. Butterfield Oxidative modification and down-regulation of Pin1 in Alzheimers disease hippocampus: a redox proteomics analysis Neurobiol. Aging 27 2006 918 925
55. L. Segat, A. Pontillo, G. Annoni, D. Trabattoni, C. Vergani, M. Clerici, B. Arosio, and S. Crovella PIN1 promoter polymorphisms are associated with Alzheimers disease Neurobiol. Aging 28 2007 69 74
56. E.M. Wijsman, E.W. Daw, C.E. Yu, H. Payami, E.J. Steinbart, D. Nochlin, E.M. Conlon, T.D. Bird, and G.D. Schellenberg Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2 Am. J. Hum. Genet. 75 2004 398 409
57. D.A. Butterfield, H.M. Abdul, W. Opii, S.F. Newman, G. Joshi, M.A. Ansari, and R. Sultana Pin1 in Alzheimers disease J. Neurochem. 98 2006 1697 1706
58. X.Z. Zhou, O. Kops, A. Werner, P.J. Lu, M. Shen, G. Stoller, G. Küllertz, M. Stark, G. Fischer, and K.P. Lu Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and Tau proteins Mol. Cell 6 2000 873 883
59. L. Pastorino, A. Sun, P.J. Lu, X.Z. Zhou, M. Balastik, G. Finn, G. Wulf, J. Lim, S.H. Li, X. Li, W. Xia, L.K. Nicholson, and K.P. Lu The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production Nature 440 2006 528 534
60. E.M. Reiman, K. Chen, X. Liu, D. Bandy, M. Yu, W. Lee, N. Ayutyanont, J. Keppler, S.A. Reeder, J.B. Langbaum, G.E. Alexander, W.E. Klunk, C.A. Mathis, J.C. Price, H.J. Aizenstein, S.T. DeKosky, and R.J. Caselli Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimers disease Proc. Natl. Acad. Sci. USA 106 2009 6820 6825
61. J.M. Castellano, J. Kim, F.R. Stewart, H. Jiang, R.B. DeMattos, B.W. Patterson, A.M. Fagan, J.C. Morris, K.G. Mawuenyega, C. Cruchaga, A.M. Goate, K.R. Bales, S.M. Paul, R.J. Bateman, and D.M. Holtzman Human apoE isoforms differentially regulate brain amyloid-β peptide clearance Sci. Transl. Med. 3 2011 89-57
62. K.R. Bales, F. Liu, S. Wu, S. Lin, D. Koger, C. DeLong, J.C. Hansen, P.M. Sullivan, and S.M. Paul Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice J. Neurosci. 29 2009 6771 6779
63. C.M. Lauderback, J. Kanski, J.M. Hackett, N. Maeda, M.S. Kindy, and D.A. Butterfield Apolipoprotein E modulates Alzheimers Aβ(1-42)-induced oxidative damage to synaptosomes in an allele-specific manner Brain Res. 924 2002 90 97
64. P. Osenkowski, W. Ye, R. Wang, M.S. Wolfe, and D.J. Selkoe Direct and potent regulation of γ-secretase by its lipid microenvironment J. Biol. Chem. 283 2008 22529 22540
65. K. Aoki, T. Uchihara, N. Sanjo, A. Nakamura, K. Ikeda, K. Tsuchiya, and Y. Wakayama Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction Stroke 34 2003 875 880
66. W.J. Brecht, F.M. Harris, S. Chang, I. Tesseur, G.Q. Yu, Q. Xu, J. Dee Fish, T. Wyss-Coray, M. Buttini, L. Mucke, R.W. Mahley, and Y. Huang Neuron-specific apolipoprotein e4 proteolysis is associated with increased Tau phosphorylation in brains of transgenic mice J. Neurosci. 24 2004 2527 2534
67. R.W. Mahley, K.H. Weisgraber, and Y. Huang Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimers disease Proc. Natl Acad. Sci. USA 103 2006 5644 5651
68. J. Zhang, S.A. Cicero, L. Wang, R.R. Romito-DiGiacomo, Y. Yang, and K. Herrup Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons Proc. Natl. Acad. Sci. USA 105 2008 8772 8777
69. S. Cicero, and K. Herru Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation J. Neurosci. 25 2005 9658 9668
70. J. Lew, Z. Qi, Q. Huang, H. Paudel, I. Matsuura, M. Matsshita, X. Zhu, and J.I. Wang Structure, function, and regulation of neuronal cdc2-like protein kinase Neurobiol. Aging 16 1995 263 270
71. K.Y. Lee, A.W. Clark, J.L. Rosales, K. Chapman, T. Fung, and R. Johnston Elevated neuronal Cdc2-like kinase activity in the Alzheimer disease brain Neurosci. Res. 34 1999 21 29
72. G.N. Patrick, L. Zukerberg, M. Nikolic, S. Monte, P. Dikkesk, and L.H. Tsai Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration Nature 402 2000 615 622
73. A. Alvarez, J.P. Munoz, and R.B.A. Maccioni Cdk5-p35 stable complex is involved in the β-amyloid-induced deregulation of Cdk5 activity in hippocampal neurons Exp. Cell Res. 264 2001 266 274
74. H.C. Tseng, Y. Zhou, Y. Shen, and L.H.A. Tsai Survey of Cdk5 activator p35 and p25 levels in Alzheimers disease brains FEBS Lett. 523 2002 58 62
75. T. Tsujia, S. Shimohamaa, J. Kimuraa, and K. Shimizub m-Calpain (calcium-activated neutral proteinase) in Alzheimers disease brains Neurosci. Lett. 248 1998 109 112
76. K.H. Chang, Y. Pablo, H.P. Lee, H.G. Lee, M. Smith, and K. Shah Cdk5 is a major regulator of p38 cascade: relevance to neurotoxicity in Alzheimers disease J. Neurochem. 113 2010 1221 1229
77. J.C. Lee, J.T. Laydon, P.C. McDonnell, T.F. Gallagher, S. Kumar, D. Green, D. McNulty, M.J. Blumenthal, J.R. Heys, and S.W. Landvatter A protein kinase involved in the regulation of inflammatory cytokine biosynthesis Nature 372 1994 22 29
78. I. Dolado, A. Swat, N. Ajenjo, G. De Vita, A. Cuadrado, and A.R. Nebreda p38α MAP kinase as a sensor of reactive oxygen species in tumorigenesis Cancer Cell 11 2007 191 205
79. L. Munoz, and A.J. Ammit Targeting p38 MAPK pathway for the treatment of Alzheimers disease Neuropharmacology 58 2010 561 568
80. J.J. Pei, E. Braak, H. Braak, I. Grundke-Iqbal, K. Iqbal, B. Winblad, and R.F. Cowburn Localization of active forms of C-jun kinase (JNK) and p38 kinase in Alzheimers disease brains at different stages of neurofibrillary degeneration J. Alzheimers Dis. 3 2001 41 48
81. X. Zhu, C.A. Rottkamp, A. Hartzler, Z. Sun, A. Takeda, H. Boux, S. Shimohama, G. Perry, and M.A. Smith Activation of MKK6, an upstream activator of p38, in Alzheimers disease J. Neurochem. 79 2001 311 318
82. K. Hensley, R.A. Floyd, N.Y. Zheng, R. Nael, K.A. Robinson, X. Nguyen, Q.N. Pye, C.A. Stewart, J. Geddes, W.R. Markesbery, E. Patel, G.V. Johnson, and G. Bing p38 kinase is activated in the Alzheimers disease brain J. Neurochem. 72 1999 2053 2058
83. C.H. Reynolds, A.R. Nebreda, G.M. Gibb, M.A. Utton, and B.H. Anderton Reactivating kinase/p38 phosphorylates Tau protein in vitro J. Neurochem. 69 1997 191 198
84. C.H. Reynolds, J.C. Betts, W.P. Blackstock, A.R. Nebreda, and B.H. Anderton Phosphorylation sites on Tau identified by nanoelectrospray mass spectrometry: differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun N-terminal kinase and P38, and glycogen synthase kinase-3β J. Neurochem. 74 2000 1587 1595
85. I. Churcher Tau therapeutic strategies for the treatment of Alzheimers disease Curr. Top. Med. Chem. 6 2006 579 595
86. C. Feijoo, D.G. Campbell, R. Jakes, M. Goedert, and A. Cuenda Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly J. Cell Sci. 118 2005 397 408
87. M. Goedert, M. Hasegawa, R. Jakes, S. Lawler, A. Cuenda, and P. Cohen Phosphorylation of microtubule-associated protein Tau by stress-activated protein kinases FEBS Lett. 409 1997 7 62
88. I. Kelleher, C. Garwood, D.P. Hanger, B.H. Anderton, and W. Noble Kinase activities increase during the development of Tauopathy in hTau mice J. Neurochem. 103 2007 2256 2267
89. M.J. Savage, Y.G. Lin, J.R. Ciallella, D.G. Flood, and R.W. Scott Activation of c-Jun N-terminal kinase and p38 in an Alzheimers disease model is associated with amyloid deposition J. Neurosci. 22 2002 3376 3385
90. E. Giraldo, A. Lloret, T. Fuchsberger, and J. Viña Aβ and Tau toxicities in Alzheimers are linked via oxidative stress-induced p38 activation: protective role of vitamin E Redox Biol 2 2014 873 877