Dysregulation of protein phosphorylation/dephosphorylation in Alzheimer's disease: A therapeutic target

Journal of Biomedicine and Biotechnology

Volumn 2006, Issue , 2006, Pages

  Gong, Cheng Xin ^a   Liu, Fei ^a   Grundke Iqbal, Inge ^a   Iqbal, Khalid ^a  

^a NEW YORK STATE INSTITUTE FOR BASIC RESEARCH IN DEVELOPMENTAL DISABILITIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALYCULIN A; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIN DEPENDENT KINASE 5; GLYCOGEN SYNTHASE KINASE 3BETA; MELATONIN; MEMANTINE; MITOGEN ACTIVATED PROTEIN KINASE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; OKADAIC ACID; PHOSPHOPROTEIN PHOSPHATASE 2A; PROTEIN KINASE (CALCIUM,CALMODULIN) II; TAU PROTEIN;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; BRAIN TISSUE; DEPHOSPHORYLATION; ENZYME ACTIVITY; HISTOPATHOLOGY; HUMAN; MICROTUBULE; NERVE DEGENERATION; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REVIEW;

EID: 33646020719     PISSN: 11107243     EISSN: 11107251     Source Type: Journal    
DOI: 10.1155/JBB/2006/31825     Document Type: Review

References (159)

1. G G Glenner C W Wong Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochemical and Biophysical Research Communications 120 1984 3 885 890 6375662
2. C L Masters G Simms N A Weinman Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proceedings of the National Academy of Sciences of the United States of America 82 1985 12 4245 4249 3159021
3. I Grundke-Iqbal K Iqbal M Quinlan Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. The Journal of Biological Chemistry 261 1986 13 6084 6089 3084478
4. I Grundke-Iqbal K Iqbal Y C Tung Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences of the United States of America 83 1986 13 4913 4917 3088567
5. B E Tomlinson G Blessed M Roth Observations on the brains of demented old people. Journal of the Neurological Sciences 11 1970 3 205 242 5505685
6. I Alafuzoff K Iqbal H Friden R Adolfsson B Winblad Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis. Acta Neuropathologica (Berl) 74 1987 3 209 225 3673513
7. D W Dickson J Farlo P Davies Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. The American Journal of Pathology 132 1988 1 86 101 2456021
8. P V Arriagada J H Growdon E T Hedley-Whyte Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42 1992 3 pt 1 631 639 1549228
9. K P Riley D A Snowdon W R Markesbery Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Annals of Neurology 51 2002 5 567 577 12112102
10. D Yancopoulou M G Spillantini Tau protein in familial and sporadic diseases. Neuromolecular Medicine 4 2003 1-2 37 48 14528051
11. K Iqbal C Alonso Adel S Chen Tau pathology in Alzheimer disease and other tauopathies. Biochimica et Biophysica Acta 1739 2005 2-3 198 210 15615638
12. M Hutton C L Lendon P Rizzu Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393 1998 6686 702 705 9641683
13. P Poorkaj T D Bird E Wijsman Tau is a candidate gene for chromosome 17 frontotemporal dementia. Annals of Neurology 43 1998 6 815 825 9629852
14. M G Spillantini J R Murrell M Goedert Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proceedings of the National Academy of Sciences of the United States of America 95 1998 13 7737 7741 9636220
15. K Iqbal I Grundke-Iqbal T Zaidi Defective brain microtubule assembly in Alzheimer's disease. Lancet 2 1986 8504 421 426 2874414
16. C Alonso Adel T Zaidi I Grundke-Iqbal Role of abnormally phosphorylated τ in the breakdown of microtubules in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 91 1994 12 5562 5566 8202528
17. C Alonso Adel T Zaidi M Novak Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proceedings of the National Academy of Sciences of the United States of America 98 2001 12 6923 6928 11381127
18. C Alonso Adel T Zaidi M Novak Interaction of tau isoforms with Alzheimer's disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein. The Journal of Biological Chemistry 276 2001 41 37967 37973 11495914
19. C Alonso Adel A Mederlyova M Novak Promotion of hyperphosphorylation by frontotemporal dementia tau mutations. The Journal of Biological Chemistry 279 2004 33 34873 34881 15190058
20. J J Lucas F Hernandez P Gomez-Ramos Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. The EMBO Journal 20 2001 1-2 27 39 11226152
21. M Perez F Hernandez A Gomez-Ramos Formation of aberrant phosphotau fibrillar polymers in neural cultured cells. European Journal of Biochemistry 269 2002 5 1484 1489 11874463
22. T Fath J Eidenmuller R Brandt Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer's disease. The Journal of Neuroscience 22 2002 22 9733 9741 12427828
23. G R Jackson M Wiedau-Pazos T K Sang Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron 34 2002 4 509 519 12062036
24. N H Stemberger L A Sternberger J Ulrich Aberrant neurofilament phosphorylation in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 82 1985 4274 4276
25. L Ulloa E M de Garcini P Gòmez-Ramos Microtubule-associated protein MAP1B showing a fetal phosphorylation pattern is present in sites of neurofibrillary degeneration in brains of Alzheimer's disease patients. Molecular Brain Research 26 1994 1-2 113 122 7854037
26. S Vijayan E El-Akkad I Grundke-Iqbal A pool of β-tubulin is hyperphosphorylated at serine residues in Alzheimer disease brain. FEBS Letters 509 2001 3 375 381 11749959
27. J-Z Wang Y C Tung Y Wang Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid-treated SY5Y cells. FEBS Letters 507 2001 1 81 87 11682063
28. M D Weingarten A H Lockwood S-Y Hwo A protein factor essential for microtubule assembly. Proceedings of the National Academy of Sciences of the United States of America 72 1975 5 1858 1862 1057175
29. V M Lee B J Balin L Jr Otvos J Q Trojanowski A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science 251 1991 4994 675 678 1899488
30. R L Neve P Harris K S Kosik 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 Research 387 1986 3 271 280 3103857
31. M Goedert M G Spillantini R Jakes Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 3 1989 4 519 526 2484340
32. G Lee R L Neve K S Kosik The microtubule binding domain of tau protein. Neuron 2 1989 6 1615 1624 2516729
33. B L Goode S C Feinstein Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau. The Journal of Cell Biology 124 1994 5 769 782 8120098
34. D Panda B L Goode S C Feinstein Kinetic stabilization of microtubule dynamics at steady state by tau and microtubule-binding domains of tau. Biochemistry 34 1995 35 11117 11127 7669769
35. N Hirokawa Y Shiomura S Okabe Tau proteins: the molecular structure and mode of binding on microtubules. The Journal of Cell Biology 107 1988 4 1449 1459 3139677
36. R Brandt J Leger G Lee Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain. The Journal of Cell Biology 131 1995 5 1327 1340 8522593
37. M A Utton G M Gibb I D Burdett Functional differences of tau isoforms containing 3 or 4 C-terminal repeat regions and the influence of oxidative stress. The Journal of Biological Chemistry 276 2001 36 34288 34297 11438517
38. P M Stanford C E Shepherd G M Halliday Mutations in the tau gene that cause an increase in three repeat tau and frontotemporal dementia. Brain 126 2003 pt 4 814 826 12615641
39. K S Kosik L D Orecchio S Bakalis Developmentally regulated expression of specific tau sequences. Neuron 2 1989 4 1389 1397 2560640
40. M Goedert R Jakes Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. The EMBO Journal 9 1990 13 4225 4230 2124967
41. Y Tatebayashi N Haque Y C Tung Role of tau phosphorylation by glycogen synthase kinase-3β in the regulation of organelle transport. Journal of Cell Science 117 2004 pt 9 1653 1663 15075227
42. A Ebneth R Godemann K Stamer Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease. The Journal of Cell Biology 143 1998 3 777 794 9813097
43. T Ishihara M Hong B Zhang Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24 1999 3 751 762 10595524
44. K Spittaels C Van den Haute J Van Dorpe Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. The American Journal of Pathology 155 1999 6 2153 2165 10595944
45. J Lewis E McGowan J Rockwood Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nature Genetics 25 2000 4 402 405 10932182
46. A Probst J Gotz K H Wiederhold Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathologica (Berl) 99 2000 5 469 481 10805089
47. A Rendon D Jung V Jancsik Interaction of microtubules and microtubule-associated proteins (MAPs) with rat brain mitochondria. The Biochemical Journal 269 1990 2 555 556 2386493
48. T Kampers P Friedhoff J Biernat RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments. FEBS Letters 399 1996 3 344 349 8985176
49. Q Hua R Q He N Haque Microtubule associated protein tau binds to double-stranded but not single-stranded DNA. Cellular and Molecular Life Sciences 60 2003 2 413 421 12678504
50. G Lee S T Newman D L Gard H Band G Panchamoorthy Tau interacts with src-family non-receptor tyrosine kinases. Journal of Cell Science 111 1998 pt 21 3167 3177 9763511
51. K Bhaskar S-H Yen G Lee Disease-related modifications in tau affect the interaction between Fyn and Tau. The Journal of Biological Chemistry 280 2005 42 35119 35125 16115884
52. A Jaspert R Fahsold H Grehl Myotonic dystrophy: correlation of clinical symptoms with the size of the CTG trinucleotide repeat. Journal of Neurology 242 1995 2 99 104 7707098
53. S M Jenkins G V Johnson Tau complexes with phospholipase C-gamma in situ. NeuroReport 9 1998 1 67 71 9592050
54. D W Cleveland S Y Hwo M W Kirschner Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. Journal of Molecular Biology 116 1977 2 227 247 146092
55. G Lindwall R D Cole Phosphorylation affects the ability of tau protein to promote microtubule assembly. The Journal of Biological Chemistry 259 1984 8 5301 5305 6425287
56. H Ksiezak-Reding W K Liu S H Yen Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments. Brain Research 597 1992 2 209 219 1472994
57. E Köpke Y-C Tung S Shaikh Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. The Journal of Biological Chemistry 268 1993 32 24374 24384 8226987
58. A Kenessey S H Yen The extent of phosphorylation of fetal tau is comparable to that of PHF-tau from Alzheimer paired helical filaments. Brain Research 629 1993 1 40 46 8287279
59. E S Matsuo R W Shin M L Billingsley Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau. Neuron 13 1994 4 989 1002 7946342
60. T D Garver K A Harris R A Lehman Tau phosphorylation in human, primate, and rat brain: evidence that a pool of tau is highly phosphorylated in vivo and is rapidly dephosphorylated in vitro. Journal of Neurochemistry 63 1994 6 2279 2287 7964748
61. K Iqbal T Zaidi C Bancher Alzheimer paired helical filaments. Restoration of the biological activity by dephosphorylation. FEBS Letters 349 1994 1 104 108 8045285
62. D N Drechsel A A Hyman M H Cobb M W Kirschner Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Molecular Biology of the Cell 3 1992 10 1141 1154 1421571
63. G T Bramblett M Goedert R Jakes Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron 10 1993 6 1089 1099 8318230
64. H Yoshida Y Ihara Tau in paired helical filaments is functionally distinct from fetal tau: assembly incompetence of paired helical filament-tau. Journal of Neurochemistry 61 1993 3 1183 1186 8360683
65. J Biernat N Gustke G Drewes Phosphorylation of Ser 262strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron 11 1993 1 153 163 8393323
66. C Alonso Adel I Grundke-Iqbal K Iqbal Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nature Medicine 2 1996 7 783 787 8673924
67. J-Z Wang C-X Gong T Zaidi Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. The Journal of Biological Chemistry 270 1995 9 4854 4860 7876258
68. J-Z Wang I Grundke-Iqbal K Iqbal Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer's disease. Nature Medicine 2 1996 8 871 875 8705855
69. C-X Gong T Lidsky J Wegiel Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. The Journal of Biological Chemistry 275 2000 8 5535 5544 10681533
70. S Khatoon I Grundke-Iqbal K Iqbal Brain levels of microtubule-associated protein tau are elevated in Alzheimer's disease: a radioimmuno-slot-blot assay for nanograms of the protein. Journal of Neurochemistry 59 1992 2 750 753 1629745
71. S Khatoon I Grundke-Iqbal K Iqbal Levels of normal and abnormally phosphorylated tau in different cellular and regional compartments of Alzheimer disease and control brains. FEBS Letters 351 1994 1 80 84 8076698
72. R Kohnken K Buerger R Zinkowski Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients. Neuroscience Letters 287 2000 3 187 190 10863026
73. K Ishiguro H Ohno H Arai Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease. Neuroscience Letters 270 1999 2 91 94 10462105
74. H Hampel K Buerger R Kohnken Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231. Annals of Neurology 49 2001 4 545 546 11310639
75. H Hampel K Buerger R Zinkowski Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Archives of General Psychiatry 61 2004 1 95 102 14706948
76. L Parnetti A Lanari S Amici CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Neurological Sciences 22 2001 1 77 78 11487210
77. E Vanmechelen E Van Kerschaver K Blennow K Iqbal S Sissodia B Winblad CSF-phospho-tau (181P) as a promising marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics John Wiley & Sons Chichester, UK 2001 285 291
78. N Itoh H Arai K Urakami Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease. Annals of Neurology 50 2001 2 150 156 11506396
79. Y Y Hu S S He X C Wang Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients : an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay. The American Journal of Pathology 160 2002 4 1269 1278 11943712
80. K Buerger R Zinkowski S J Teipel Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Archives of Neurology 59 2002 8 1267 1272 12164722
81. M Goedert M G Spillantini N J Cairns Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8 1992 1 159 168 1530909
82. C-X Gong F Liu I Grundke-Iqbal Post-translational modifications of tau protein in Alzheimer's disease. Journal of Neural Transmission 112 2005 6 813 838 15517432
83. C-X Gong T J Singh I Grundke-Iqbal Phosphoprotein phosphatase activities in Alzheimer disease brain. Journal of Neurochemistry 61 1993 3 921 927 8395566
84. C-X Gong S Shaikh J-Z Wang T Zaidi Phosphatase activity toward abnormally phosphorylated τ: decrease in Alzheimer disease brain. Journal of Neurochemistry 65 1995 2 732 738 7616230
85. V Vogelsberg-Ragaglia T Schuck J Q Trojanowski PP2A mRNA expression is quantitatively decreased in Alzheimer's disease hippocampus. Experimental Neurology 168 2001 2 402 412 11259128
86. J F Loring X Wen J M Lee A gene expression profile of Alzheimer's disease. DNA and Cell Biology 20 2001 11 683 695 11788046
87. E Sontag A Luangpirom C Hladik Altered expression levels of the protein phosphatase 2A ABαC enzyme are associated with Alzheimer disease pathology. Journal of Neuropathology and Experimental Neurology 63 2004 4 287 301 15099019
88. F Liu I Grundke-Iqbal K Iqbal Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. The European Journal of Neuroscience 22 2005 8 1942 1950 16262633
89. F Liu K Iqbal I Grundke-Iqbal Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease. The Journal of Biological Chemistry 280 2005 3 1790 1796 15546861
90. R Hoffmann V M Lee S Leight Unique Alzheimer's disease paired helical filament specific epitopes involve double phosphorylation at specific sites. Biochemistry 36 1997 26 8114 8124 9201960
91. M Hasegawa R Jakes R Crowther Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein. FEBS Letters 384 1996 1 25 30 8797796
92. T Bussiere P R Hof C Mailliot Phosphorylated serine422 on tau proteins is a pathological epitope found in several diseases with neurofibrillary degeneration. Acta Neuropathologica (Berl) 97 1999 3 221 230 10090668
93. G Lee R Thangavel V M Sharma Phosphorylation of tau by fyn: implications for Alzheimer's disease. The Journal of Neuroscience 24 2004 9 2304 2312 14999081
94. R Williamson T Scales B R Clark Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-β peptide exposure: involvement of Src family protein kinases. The Journal of Neuroscience 22 2002 1 10 20 11756483
95. P Derkinderen T M Scales D P Hanger Tyrosine 394 is phosphorylated in Alzheimer's paired helical filament tau and in fetal tau with c-Abl as the candidate tyrosine kinase. The Journal of Neuroscience 25 2005 28 6584 6593 16014719
96. M Rapoport H N Dawson L I Binder Tau is essential to beta -amyloid-induced neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America 99 2002 9 6364 6369 11959919
97. J Brich F S Shie B W Howell Genetic modulation of tau phosphorylation in the mouse. The Journal of Neuroscience 23 2003 1 187 192 12514215
98. V MY Lee M Goedert J Q Trojanowski Neurodegenerative tauopathies. Annual Review of Neuroscience 24 2001 1121 1159 11520930
99. C Bancher C Brunner H Lassman Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Research 477 1989 1-2 90 99 2495152
100. C Bancher I Grundke-Iqbal K Iqbal Abnormal phosphorylation of tau precedes ubiquitination in neurofibrillary pathology of Alzheimer disease. Brain Research 539 1991 1 11 18 1849776
101. E Braak H Braak E-M Mandelkow A sequence of cytoskeletal changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathologica 87 1994 544 567
102. A Sengupta J Kabat M Novak Maximal inhibition of tau binding to microtubules requires the phosphorylation of tau at both Thr 231 and Ser 262. Neurobiology of Aging 19S 1998 S124 S524
103. A Schneider J Biernat M von Bergen Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 38 1999 12 3549 3558 10090741
104. A Abraha N Ghoshal T C Gamblin C-terminal inhibition of tau assembly in vitro and in Alzheimer's disease. Journal of Cell Science 113 2000 pt 21 3737 3745 11034902
105. C Haase J Stieler T Arendt Pseudophosphorylation of tau protein alters its ability for self-aggregation. Journal of Neurochemistry 88 2004 6 1509 1520 15009652
106. A Ferrari F Hoerndli T Baechi Beta-amyloid induces paired helical filament-like tau filaments in tissue culture. The Journal of Biological Chemistry 278 2003 41 40162 40168 12893817
107. A Harada K Oguchi S Okabe Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 369 1994 6480 488 491 8202139
108. C Alonso Adel I Grundke-Iqbal H S Barra Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau. Proceedings of the National Academy of Sciences of the United States of America 94 1997 1 298 303 8990203
109. F Hernandez J Borrell C Guaza Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. Journal of Neurochemistry 83 2002 6 1529 1533 12472906
110. V MY Lee T K Kenyon J Q Trojanowski Transgenic animal models of tauopathies. Biochimica et Biophysica Acta 1739 2005 2-3 251 259 15615643
111. R Kayed E Head J L Thompson Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300 2003 5618 486 489 12702875
112. A Sanbe H Osinska C Villa Reversal of amyloid-induced heart disease in desmin-related cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America 102 2005 38 13592 13597 16155124
113. L F Lau J B Schachter P A Seymour Tau protein phosphorylation as a therapeutic target in Alzheimer's disease. Current Topics in Medicinal Chemistry 2 2002 4 395 415 11966463
114. Q Tian J Wang Role of serine/threonine protein phosphatase in Alzheimer's disease. Neurosignals 11 2002 5 262 269 12566927
115. G V Johnson W H Stoothoff Tau phosphorylation in neuronal cell function and dysfunction. Journal of Cell Science 117 2004 pt 24 5721 5729 15537830
116. M Goedert R Jakes Z Qi Protein phosphatase 2A is the major enzyme in brain that dephosphorylates tau protein phosphorylated by proline-directed protein kinases or cyclic AMP-dependent protein kinase. Journal of Neurochemistry 65 1995 6 2804 2807 7595582
117. E Sontag V Nunbhakdi-Craig G Lee Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron 17 1996 6 1201 1207 8982166
118. E Sontag V Nunbhakdi-Craig G Lee Molecular interactions among protein phosphatase 2A, tau, and microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies. The Journal of Biological Chemistry 274 1999 36 25490 25498 10464280
119. M Bennecib C-X Gong I Grundke-Iqbal 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 Letters 485 2000 1 87 93 11086171
120. S Kins A Crameri D R Evans Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. The Journal of Biological Chemistry 276 2001 41 38193 38200 11473109
121. F Liu I Grundke-Iqbal K Iqbal Truncation and activation of calcineurin A by calpain l in Alzheimer disease brain. The Journal of Biological Chemistry 280 45 2005 37755 37762
122. A Sengupta Q Wu I Grundke-Iqbal Potentiation of GSK-3-catalyzed Alzheimer-like phosphorylation of human tau by cdk5. Molecular and Cellular Biochemistry 167 1997 1-2 99 105 9059986
123. J-Z Wang Q Wu A Smith τ is phosphorylated by GSK-3 at several sites found in Alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by A-kinase. FEBS Letters 436 1998 1 28 34 9771888
124. S J Liu J Y Zhang H L Li Tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain. The Journal of Biological Chemistry 279 2004 48 50078 50088 15375165
125. J H Cho G V Johnson Glycogen synthase kinase 3beta phosphorylates tau at both primed and unprimed sites. Differential impact on microtubule binding. The Journal of Biological Chemistry 278 2003 1 187 193 12409305
126. J H Cho G V Johnson Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta (GSK3beta) plays a critical role in regulating tau's ability to bind and stabilize microtubules. Journal of Neurochemistry 88 2004 2 349 358 14690523
127. L Sun X Wang S Liu Bilateral injection of isoproterenol into hippocampus induces Alzheimer-like hyperphosphorylation of tau and spatial memory deficit in rat. FEBS Letters 579 2005 1 251 258 15620722
128. S J Liu A H Zhang H L Li Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory. Journal of Neurochemistry 87 2003 6 1333 1344 14713290
129. L Baki J Shioi P Wen PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. The EMBO Journal 23 2004 13 2586 2596 15192701
130. X Li F Lu Q Tian Activation of glycogen synthase kinase-3 induces Alzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture. Journal of Neural Transmission 113 2006 1 93 102 15959856
131. Y Q Deng G G Xu P Duan Effects of melatonin on wortmannin-induced tau hyperphosphorylation. Acta Pharmacologica Sinica 26 2005 5 519 526 15842767
132. G N Patrick L Zukerberg M Nikolic Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402 1999 6762 615 622 10604467
133. B C Yoo G Lubec p25 protein in neurodegeneration. Nature 411 2001 6839 763 764 11459045
134. S Taniguchi Y Fujita S Hayashi Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains. FEBS Letters 489 2001 1 46 50 11231011
135. K C Nguyen J L Rosales M Barboza Controversies over p25 in Alzheimer's disease. Journal of Alzheimer's Disease 4 2002 2 123 126 12214136
136. A Tandon H Yu L Wang Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles. Journal of Neurochemistry 86 2003 3 572 581 12859671
137. T Tanaka J Zhong K Iqbal The regulation of phosphorylation of tau in SY5Y neuroblastoma cells: the role of protein phosphatases. FEBS Letters 426 1998 2 248 254 9599018
138. M Bennecib C-X Gong I Grundke-Iqbal Inhibition of PP-2A upregulates CaMKII in rat forebrain and induces hyperphosphorylation of tau at Ser 262/356. FEBS Letters 490 2001 1-2 15 22 11172803
139. J-J Pei C-X Gong W An Okadaic-acid-induced inhibition of protein phosphatase 2A produces activation of mitogen-activated protein kinases ERK1/2, MEK1/2, and p70 S6, similar to that in Alzheimer's disease. The American Journal of Pathology 163 2003 3 845 858 12937126
140. S Kins P Kurosinski R M Nitsch J Gotz Activation of the ERK and JNK signaling pathways caused by neuron-specific inhibition of PP2A in transgenic mice. The American Journal of Pathology 163 2003 3 833 843 12937125
141. W-L An R F Cowburn L Li Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease. The American Journal of Pathology 163 2003 2 591 607 12875979
142. H Tanimukai I Grundke-Iqbal K Iqbal Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer's disease. The American Journal of Pathology 166 2005 6 1761 1771 15920161
143. C S Arnold G V Johnson R N Cole The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine. The Journal of Biological Chemistry 271 1996 46 28741 28744 8910513
144. T Lefebvre S Ferreira L Dupont-Wallois Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins - a role in nuclear localization. Biochimica et Biophysica Acta 1619 2003 2 167 176 12527113
145. F Liu K Iqbal I Grundke-Iqbal O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 101 2004 29 10804 10809 15249677
146. F I Comer G W Hart O-Glycosylation of nuclear and cytosolic proteins. Dynamic interplay between O-GlcNAc and O-phosphate. The Journal of Biological Chemistry 275 2002 38 29179 29182 10924527
147. L A Robertson K L Moya K C Breen The potential role of tau protein O-glycosylation in Alzheimer's disease. Journal of Alzheimer's Disease 6 2004 5 489 495 15505370
148. C-X Gong F Liu I Grundke-Iqbal Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylation. Journal of Alzheimer's Disease. 2006; in press
149. M Takahishi Y Tsumioka T Yamada Glycosylation of microtubule-associated protein tau in Alzheimer's disease brain. Acta Neuropathologica (Berl) 97 1999 6 635 641 10378383
150. F Liu T Zaidi I Grundke-Iqbal Role of glycosylation in hyperphosphorylation of tau in Alzheimer's disease. FEBS Letters 512 2002 1-3 101 106 11852060
151. F Liu T Zaidi I Grandke-Iqbal Aberrant glycosylation modulates phosphorylation of tau by protein kinase A and dephosphorylation of tau by protein phosphatase 2A and 5. Neuroscience 115 2002 3 829 837 12435421
152. F Liu I Grundke-Iqbal K Iqbal Involvement of aberrant glycosylation in phosphorylation of tau by cdk5 and GSK-3β FEBS Letters 530 2002 1-3 209 214 12387894
153. B Winblad N Poritis Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). International Journal of Geriatric Psychiatry 14 1999 2 135 146 10885864
154. B Reisberg A Doody A Stoffler Memantine in moderate-to-severe Alzheimer's disease. The New England Journal of Medicine 348 2003 14 1333 1341 12672860
155. L Li A Sengupta N Haque Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration. FEBS Letters 566 2004 1-3 261 269 15147906
156. S P Li Y Q Deng Y P Wang Melatonin protects SH-SY5Y neuroblastoma cells from calyculin A-induced neurofilament impairment and neurotoxicity. Journal of Pineal Research 36 2004 3 186 191 15009509
157. X C Li Z F Wang J X Zhang Effect of melatonin on calyculin A-induced tau hyperphosphorylation. European Journal of Pharmacology 510 2005 1-2 25 30 15740721
158. L Q Zhu S H Wang Z Q Ling Effect of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rat. Journal of Pineal Research 37 2004 2 71 77 15298664
159. D L Wang Z Q Ling F Y Cao Melatonin attenuates isoproterenol-induced protein kinase A overactivation and tau hyperphosphorylation in rat brain. Journal of Pineal Research 37 2004 1 11 16 15230863