Tau gene alternative splicing: Expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1739, Issue 2, 2005, Pages 91-103

  Andreadis, Athena ^a,b  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

Alternative splicing; MAP tau; Neurodegeneration; Neuronal structure and function

Indexed keywords

ISOPROTEIN; TAU PROTEIN;

ALTERNATIVE RNA SPLICING; AMINO TERMINAL SEQUENCE; BRAIN; CARBOXY TERMINAL SEQUENCE; CELL MIGRATION; CELL STRUCTURE; CENTRAL NERVOUS SYSTEM; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DEMENTIA; DISEASE SEVERITY; EXON; GENE CONTROL; GENE EXPRESSION; GENE FUNCTION; GENE LOCATION; GENE MUTATION; GENE STRUCTURE; HUMAN; MICROTUBULE; NERVE CELL; NERVE DEGENERATION; NERVE FIBER; NEUROFIBRILLARY TANGLE; NEUROPATHY; NONHUMAN; PERIPHERAL NERVOUS SYSTEM; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; TISSUE DISTRIBUTION; TRANSGENIC MOUSE;

ALTERNATIVE SPLICING; AMINO ACID SEQUENCE; ANIMALS; BASE SEQUENCE; BRAIN; GENE EXPRESSION REGULATION; HUMANS; MICE; MOLECULAR SEQUENCE DATA; NEURODEGENERATIVE DISEASES; PROTEIN ISOFORMS; TAU PROTEINS;

MUS MUSCULUS;

EID: 10944272640     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2004.08.010     Document Type: Review

References (108)

1. P.A. Sharp Split genes and RNA splicing Cell 77 1994 805 815
2. S.M. Mount A catalogue of splice junction sequences Nucleic Acids Res. 10 1982 459 472
3. G. Neubauer, A. King, J. Rappsilber, C. Calvio, M. Watson, P. Ajuh, J. Sleeman, A. Lamond, and M. Mann Mass spectometry and EST-database searching allows characterization of the multiprotein spliceosome complex Nat. Genet. 20 1998 46 50
4. R. Reed Initial splice-site recognition and pairing during pre-mRNA splicing Curr. Opin. Genet. Dev. 6 1996 215 220
5. C.W. Smith, E.B. Porro, J.G. Patton, and B. Nadal-Ginard Scanning from an independently specified branch point defines the 3′ splice site of mammalian introns Nature 342 1989 243 247
6. S.M. Berget Exon recognition in vertebrate splicing J. Biol. Chem. 270 1995 2411 2414
7. C.W. Smith, and J. Valcárcel Alternative pre-mRNA splicing: the logic of combinatorial control Trends Biochem. Sci. 25 2000 381 388
8. T.A. Thanaraj, and S. Stamm Prediction and statistical analysis of alternatively spliced exons Prog. Mol. Subcell. Biol. 31 2003 1 31
9. C.J. Lee, and K. Irizarry Alternative splicing in the nervous system: an emerging source of diversity and regulation Biol. Psychiatry 54 2003 771 776
10. B.J. Blencowe Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases Trends Biochem. Sci. 25 2000 106 110
11. H.X. Liu, M. Zhang, and A.R. Krainer Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins Genes Dev. 12 1998 1998 2012
12. L.R. Coulter, M.A. Landree, and T.A. Cooper Identification of a new class of exonic splicing enhancers by in vivo selection Mol. Cell. Biol. 17 1997 2143 2150
13. N.A. Faustino, and T.A. Cooper Pre-mRNA splicing and human disease Genes Dev. 17 2003 419 437
14. P. Stoilov, E. Meshorer, M. Gencheva, D. Glick, H. Soreq, and S. Stamm Defects in pre-mRNA processing as causes of and predisposition to diseases DNA Cell Biol. 21 2002 803 818
15. B. Chabot, M. Blanchette, I. Lapierre, and H. Branche An intron element modulating 5′ splice site selection in the hnRNP A1 pre-mRNA interacts with hnRNP A1 Mol. Cell. Biol. 17 1997 1776 1786
16. F. Del Gatto, M.C. Gesnel, and R. Breathnach The exon sequence TAGG can inhibit splicing Nucleic Acids Res. 24 1996 2017 2021
17. Q.S. Gao, J. Memmott, R. Lafyatis, S. Stamm, G. Screaton, and A. Andreadis Complex regulation of tau exon 10, whose missplicing causes frontotemporal dementia J. Neurochem. 74 2000 490 500
18. A.N. Ladd, N. Charlet, and T.A. Cooper The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing Mol. Cell. Biol. 21 2001 1285 1296
19. A. Staffa, N.H Acheson, and A. Cochrane Novel exonic elements that modulate splicing of the human fibronectin EDA exon J. Biol. Chem. 272 1997 33394 33401
20. B.R. Graveley Sorting out the complexity of SR protein functions RNA 6 2000 1197 1211
21. G. Dreyfuss, V.N. Kim, and N. Kataoka Messenger-RNA-binding proteins and the messages they carry Nat. Rev., Mol. Cell Biol. 3 2002 195 205
22. K. Musunuru Cell-specific RNA-binding proteins in human disease Trends Cardiovasc. Med. 13 2003 188 195
23. B.R. Graveley Alternative splicing: increasing diversity in the proteomic world Trends Genet. 17 2001 100 107
24. A. Herbert The four Rs of RNA-directed evolution Nat. Genet. 36 2004 19 25
25. D.L. Black Mechanisms of alternative pre-mRNA splicing Ann. Rev. Biochem. 72 2003 291 336
26. G. Ramirez, A. Alvarez, J. Garcia-Abreu, F.C. Gomes, V. Moura Neto, and R.B. Maccioni Regulatory roles of microtubule-associated proteins in neuronal morphogenesis. Involvement of the extracellular matrix Braz. J. Med. Biol. Res. 32 1999 611 618
27. M. Kempf, A. Clement, A. Faissner, G. Lee, and R. Brandt Tau binds to the distal axon early in development of polarity in a microtubule- and microfilament-dependent manner J. Neurosci. 16 1996 5583 5592
28. Y. Wang, P.A. Loomis, R.P. Zinkowski, and L.I. Binder A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau J. Cell Biol. 121 1993 257 267
29. V.C. Thurston, P. Pena, R. Pestell, and L.I. Binder Nucleolar localization of the microtubule-associated protein tau in neuroblastomas using sense and antisense transfection strategies Cell Motil. Cytoskelet. 38 1997 100 110
30. M.M. Black, T. Slaughter, S. Moshiach, M. Obrocka, and I. Fischer Tau is enriched on dynamic microtubules in the distal region of growing axons J. Neurosci. 16 1996 3601 3619
31. M. DiTella, F. Feiguin, G. Morfini, and A. Cáceres Microfilament-associated growth cone component depends upon tau for its intracellular localization Cell Motil. Cytoskelet. 29 1994 117 130
32. M. Gorath, T. Stahnke, T. Mronga, O. Goldbaum, and C. Richter-Landsberg Developmental changes of tau protein and mRNA in cultured rat brain oligodendrocytes Glia 36 2001 89 101
33. P. LoPresti, S. Szuchet, S.C. Papasozomenos, R.P. Zinkowski, and L.I. Binder Functional implications for the microtubule-associated protein tau: localization in oligodendrocytes Proc. Natl. Acad. Sci. U. S. A. 92 1995 10369 10373
34. M.L. Wei, and A. Andreadis Splicing of a regulated exon reveals additional complexity in the axonal microtubule-associated protein tau J. Neurochem. 70 1998 1346 1356
35. E.M. Mandelkow, J. Biernat, G. Drewes, N. Gustke, B. Trinczek, and E. Mandelkow Tau domains, phosphorylation and interaction with microtubules Neurobiol. Aging 16 1995 355 362
36. S. Lovestone, and C.H. Reynolds The phosphorylation of tau: a critical stage in neurodevelopment and neurodegenerative processes Neuroscience 78 1997 309 324
37. M.L. Billingsley, and R.L. Kincaid Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration Biochem. J. 323 1997 577 591
38. L. Buee, T. Bussiere, V. Buee-Scherrer, A. Delacourte, and P.R. Hof Tau protein isoforms, phosphorylation and role in neurodegenerative disorders Brain Res. Brain Res. Rev. 33 2000 95 130
39. E.M. Ingram, and M.G. Spillantini Tau gene mutations: dissecting the pathogenesis of FTDP-17 Trends Mol. Med. 8 2002 555 562
40. V. Askanas, and W.K. Engel Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms Curr. Opin. Neurol. 15 2002 525 531
41. R.L. Neve, P. Harris, K.S. Kosik, D.M. Kurnit, and T.A. Donlon 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. 387 1986 271 280
42. A. Himmler Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family Mol. Cell. Biol. 9 1989 1389 1396
43. D. Couchie, C. Mavilia, I.S. Georgieff, R.K. Liem, M.L. Shelanski, and J. Nuñez Primary structure of high molecular weight tau present in the peripheral nervous system Proc. Natl. Acad. Sci. U. S. A. 89 1992 4378 4381
44. M. Goedert, M.G. Spillantini, R. Jakes, D. Rutherford, and R.A. Crowther Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease Neuron 3 1989 519 526
45. M. Goedert, M.G. Spillantini, M.C. Potier, J. Ulrich, and R.A. Crowther 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. 8 1989 393 399
46. M. Goedert, M.G. Spillantini, and R.A. Crowther Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system Proc. Natl. Acad. Sci. U. S. A. 89 1992 1983 1987
47. J. Nuñez, and I. Fischer Microtubule-associated proteins (MAPs) in the peripheral nervous system during development and regeneration J. Mol. Neurosci. 8 1997 207 222
48. E. Sadot, R. Marx, J. Barg, L. Behar, and I. Ginzburg Complete sequence of 3′-untranslated region of tau from rat central nervous system. Implications for mRNA heterogeneity J. Mol. Biol. 241 1994 325 331
49. L. Behar, Marx.E. Sadot, J. Barg, and I. Ginzburg Cis-acting signals and trans-acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells Int. J. Dev. Neurosci. 13 1995 113 127
50. Y. Kanai, and N. Hirokawa Sorting mechanisms of tau and MAP2 in neurons-suppressed axonal transit of MAP2 and locally regulated microtubule binding Neuron 14 1995 421 432
51. A. Andreadis, B. Wagner, J.A. Broderick, and K.S. Kosik A tau promoter region without neuronal specificity J. Neurochem. 66 1996 2257 2263
52. D.G. Drubin, K.G. Miller, and D. Botstein Regulation of microtubule protein levels during cellular morphogenesis in nerve growth factor-treated PC12 cells J. Cell Biol. 107 1988 2551 2561
53. A. Himmler, D. Drechsel, M.W. Kirschner, and D.W. Martin Jr. Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains Mol. Cell. Biol. 9 1989 1381 1388
54. K.S. Kosik, L.D. Orecchio, S. Bakalis, and R.L. Neve Developmentally regulated expression of specific tau sequences Neuron 2 1989 1389 1397
55. G. Lee, N. Cowan, and M. Kirschner The primary structure and heterogeneity of tau protein from mouse brain Science 239 1988 285 288
56. M. Oblinger, A. Argasinski, J. Wong, and K.S. Kosik Tau gene expression in rat sensory neurons during development and regeneration J. Neurosci. 11 1991 2453 2459
57. M. Luo, J. Memmott, and A. Andreadis Novel isoforms of tau that lack the microtubule-binding domain J. Neurochem. 90 2004 340 351
58. G. Lee, R.L. Neve, and K.S. Kosik The microtubule binding domain of tau protein Neuron 2 1989 1615 1624
59. A. Andreadis, J.A. Broderick, and K.S. Kosik Relative exon affinities and suboptimal splice site signals lead to non-equivalence of two cassette exons Nucleic Acids Res. 23 1995 3585 3593
60. M.C. Arikan, J. Memmott, J.A. Broderick, R. Lafyatis, G. Screaton, S. Stamm, and A. Andreadis Modulation of the membrane-binding projection domain of tau protein: splicing regulation of exon 3 Brain Res. Mol. Brain Res. 101 2002 109 121
61. K. Li, M.C. Arikan, and A. Andreadis Modulation of the membrane-binding domain of tau protein: splicing regulation of exon 2 Brain Res. Mol. Brain Res. 116 2003 94 105
62. J. Wang, Q.S. Gao, Y. Wang, R. Lafyatis, S. Stamm, and A. Andreadis Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors J. Neurochem. 88 2004 1078 1090
63. J.M. Pyper, and J.B. Bolen Identification of a novel neuronal c-src exon expressed in human brain Mol. Cell. Biol. 10 1990 2035 2040
64. T.E. Golde, S. Estus, M. Usiak, L.H. Younkin, and S.G. Younkin Expression of beta amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer's disease using PCR Neuron 4 1990 253 267
65. I.S. Georgieff, R.K.H. Liem, D. Couchie, C. Mavilia, J. Nuñez, and M.L. Shelanski Expression of high molecular weight tau in the central and peripheral nervous systems J. Cell. Sci. 105 1993 729 737
66. M.L. Wei, J. Memmott, G. Screaton, and A. Andreadis The splicing determinants of a regulated exon in the axonal MAP tau reside within the exon and in its upstream intron Brain Res. Mol. Brain Res. 80 2000 207 218
67. O. Stoss, M. Olbrich, A.M. Hartmann, H. Konig, J. Memmott, A. Andreadis, and S. Stamm The STAR/GCG family protein rSLM-2 regulates the selection of alternative splice sites J. Biol. Chem. 276 2001 8665 8673
68. N. Sergeant, B. Sablonniere, S. Schraen-Maschke, A. Ghestem, C.A. Maurage, A. Wattez, P. Vermersch, and A. Delacourte Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1 Hum. Mol. Genet. 10 2001 2143 2155
69. W.K. Liu, D.W. Dickson, and S.H. Yen Heterogeneity of tau proteins in Alzheimer's disease. Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites Am. J. Pathol. 142 1993 387 394
70. M. Higuchi, T. Ishihara, B. Zhang, M. Hong, A. Andreadis, J.Q. Trojanowski, and V.M.Y. Lee Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration Neuron 35 2002 433 446
71. M. Luo, M. Leski, and A. Andreadis Tau isoforms which contain the domain encoded by exon 6 and their role in neurite elongation J. Cell. Biochem. 91 2004 880 895
72. A. Andreadis, W.M. Brown, and K.S. Kosik Structure and novel exons of the human tau gene Biochemistry 31 1992 10626 10633
73. A. Andreadis, P.E. Nisson, K.S. Kosik, and P.C. Watkins The exon trapping assay partly discriminates against alternatively spliced exons Nucleic Acids Res. 21 1993 2217 2221
74. W.T. Chen, W.K. Liu, and S.H. Yen Expression of tau exon 8 in different species Neurosci. Lett. 172 1994 167 170
75. M.J. Sobrido, B.L. Miller, N. Havlioglu, V. Zhukareva, Z. Jiang, Z.S. Nasreddine, V.M. Lee, T.W. Chow, K.C. Wilhelmsen, J.L. Cummings, J.Y. Wu, and D.H. Geschwind Novel tau polymorphisms, tau haplotypes, and splicing in familial and sporadic frontotemporal dementia Arch. Neurol. 60 2003 698 702
76. L.N. Clark, P. Poorkaj, Z. Wszolek, D.H. Geschwind, Z.S. Nasreddine, B. Miller, D. Li, H. Payami, F. Awert, K. Markopoulou, A. Andreadis, I. D'Souza, V.M. Lee, L. Reed, J.Q. Trojanowski, V. Zhukareva, T. Bird, G. Schellenberg, and K.C. Wilhelmsen Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17 Proc. Natl. Acad. Sci. U. S. A. 95 1998 13103 13107
77. M. Hutton, C.L. Lendon, P. Rizzu, M. Baker, S. Froelich, H. Houlden, S. Pickering-Brown, S. Chakraverty, A. Isaacs, and A. Grover Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17 Nature 393 1998 702 705
78. A. Grover, H. Houlden, M. Baker, J. Adamson, J. Lewis, G. Prihar, S. Pickering-Brown, K. Duff, and M. Hutton 5′ splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10 J. Biol. Chem. 274 1999 15134 15143
79. I. D'Souza, and G.D. Schellenberg Determinants of 4-repeat tau expression. Coordination between enhancing and inhibitory splicing sequences for exon 10 inclusion J. Biol. Chem. 275 2000 17700 17709
80. D. Solnick, and S.I. Lee Amount of RNA secondary structure required to induce an alternative splice Mol. Cell. Biol. 7 1987 3194 3198
81. G.C. Roberts, C. Gooding, H.Y. Mak, N.J. Proudfoot, and C.W. Smith Co-transcriptional commitment to alternative splice site selection Nucleic Acids Res. 26 1998 5568 5572
82. I. D'Souza, P. Poorkaj, M. Hong, D. Nochlin, V.M. Lee, T.D. Bird, and G.D. Schellenberg Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements Proc. Natl. Acad. Sci. U. S. A. 96 1999 5598 5603
83. I. D'Souza, and G.D. Schellenberg Tau exon 10 expression involves a bipartite intron 10 regulatory sequence and weak 5′ and 3′ splice sites J. Biol. Chem. 277 2002 26587 26599
84. P.M. Stanford, C.E. Shepherd, G.M. Halliday, W.S. Brooks, P.W. Schofield, H. Brodaty, R.N. Martins, J.B. Kwok, and P.R. Schofield Mutations in the tau gene that cause an increase in three repeat tau and frontotemporal dementia Brain 126 2003 814 826
85. J. Gotz Tau and transgenic animal models Brain Res. Brain Res. Rev. 35 2001 266 286
86. Z. Jiang, J. Cote, J.M. Kwon, A.M. Goate, and J.Y. Wu Aberrant splicing of tau pre-mRNA caused by intronic mutations associated with the inherited dementia frontotemporal dementia with parkinsonism linked to chromosome 17 Mol. Cell. Biol. 20 2000 4036 4048
87. A. Grover, M. DeTure, S.H. Yen, and M. Hutton Effects on splicing and protein function of three mutations in codon N296 of tau in vitro Neurosci. Lett. 323 2002 33 36
88. Z. Jiang, H. Tang, N. Havlioglu, X. Zhang, S. Stamm, R. Yan, and J.Y. Wu Mutations in tau gene exon 10 associated with FTDP-17 alter the activity of an exonic splicing enhancer to interact with Tra2beta1 J. Biol. Chem. 278 2003, 18997 9007
89. M.T. Nasim, T.K. Chernova, H.M. Chowdhury, B.G. Yue, and I.C. Eperon HnRNP G and Tra2beta: opposite effects on splicing matched by antagonism in RNA binding Hum. Mol. Genet. 12 2003 1337 1348
90. F. Del Gatto-Konczak, M. Olive, M.C. Gesnel, and R. Breathnach hnRNP A1 recruited to an exon in vivo can function as an exon splicing silencer Mol. Cell. Biol. 19 1999 251 260
91. A.M. Hartmann, D. Rujescu, T. Giannakouros, E. Nikolakaki, M. Goedert, E.M. Mandelkow, Q.S. Gao, A. Andreadis, and S. Stamm Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors Mol. Cell. Neurosci. 18 2001 80 90
92. R. Brandt, J. Leger, and G. Lee Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain J. Cell Biol. 131 1995 1327 1340
93. J. Chen, Y. Kanai, N.J. Cowan, and N. Hirokawa Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons Nature 360 1992 674 677
94. T.F. Frappier, I.S. Georgieff, K. Brown, and M.L. Shelanski Tau regulation of microtubule-microtubule spacing and bundling J. Neurochem. 63 1994 2288 2294
95. G. Lee, R. Thangavel, V. Sharma, J. Litersky, K. Bhaskar, S. Fang, L. Do, A. Andreadis, G. van Hoesen, and H. Ksiezak-Reding Phosphorylation of tau by fyn: implications for Alzheimer's disease J. Neurosci. 24 2004 2304 2312
96. A. Harada, K. Oguchi, S. Okabe, J. Kuno, S. Terada, T. Ohshima, R. Sato-Yoshitake, Y. Takei, T. Noda, and N. Hirokawa Altered microtubule organization in small-calibre axons of mice lacking tau protein Nature 369 1994 488 491
97. B.L. Goode, P.E. Denis, D. Panda, M.J. Radeke, H.P. Miller, L. Wilson, and S.C. Feinstein Functional interactions between the proline-rich and repeat regions of tau enhance microtubule binding and assembly Mol. Biol. Cell 8 1997 353 365
98. C.W. Liu, G. Lee, and D.G. Jay Tau is required for neurite outgrowth and growth cone motility of chick sensory neurons Cell Motil. Cytoskelet. 43 1999 232 242
99. H.N. Dawson, A. Ferreira, M.V. Eyster, N. Ghoshal, L.I. Binder, and M.P. Vitek Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice J. Cell. Sci. 11 2001 1179 1187
100. N. Shahani, and R. Brandt Functions and malfunctions of the tau proteins Cell. Mol. Life Sci. 59 2002 1668 1680
101. K.C. Wilhelmsen Chromosome 17-linked dementias Cell. Mol. Life Sci. 54 1998 920 924
102. M.T. Vanier, P. Neuville, L. Michalik, and J.F. Launay Expression of specific tau exons in normal and tumoral pancreatic acinar cells J. Cell. Sci. 111 1998 1419 1432
103. N. Canu, L. Dus, C. Barbato, M.T. Ciotti, C. Brancolini, A.M. Rinaldi, M. Novak, A. Cattaneo, A. Bradbury, and P. Calissano Tau cleavage and dephosphorylation in cerebellar granule neurons undergoing apoptosis J. Neurosci. 18 1998 7061 7074
104. L. Fasulo, G. Ugolini, M. Visintin, A. Bradbury, C. Brancolini, V. Verzillo, M. Novak, and A. Cattaneo The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis J. Neurochem. 75 2000 624 633
105. F. Esclaire, F. Terro, C. Yardin, and J. Hugon Neuronal apoptosis is associated with a decrease in tau mRNA expression NeuroReport 9 1998 1173 1177
106. P.D. Mehta, B.A. Patrick, A.J. Dalton, P.S. Aisen, M.E. Emmerling, E.A. Sersen, and H.M. Wisniewski Increased levels of tau-like protein in patients with Down syndrome Neurosci. Lett. 275 1999 159 162
107. S. Ikegami, A. Harada, and N. Hirokawa Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice Neurosci. Lett. 279 2000 129 132
108. A. Singleton, A. Myers, and J. Hardy The law of mass action applied to neurodegenerative disease: a hypothesis concerning the etiology and pathogenesis of complex diseases Hum. Mol. Genet. 13 Suppl. 1 2004 R123 R126