Inhibition of Tau aggregation in a novel caenorhabditis elegans model of tauopathy mitigates proteotoxicity

Human Molecular Genetics

Volumn 21, Issue 16, 2012, Pages 3587-3603

  Fatouros, Chronis ^a,b   Pir, Ghulam Jeelani ^c,d   Biernat, Jacek ^c,d   Koushika, Sandhya Padmanabhan ^f   Mandelkow, Eckhard ^c,d,e   Mandelkow, Eva Maria ^c,d,e   Schmidt, Enrico ^a   Baumeister, Ralf ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b International Max Planck Research School for Molecular and Cellular Biology   (Germany)

^c GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^d MAX PLANCK INSTITUTE FOR NEUROLOGICAL RESEARCH   (Germany)

^e CENTER OF ADVANCED EUROPEAN STUDIES AND RESEARCH CAESAR   (Germany)

^f TATA INSTITUTE OF FUNDAMENTAL RESEARCH   (India)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID PROTEIN; CMP16; F3DELTAK280; METHYLENE BLUE; PHENOTHIAZINE; PROTEIN INHIBITOR; SYNAPTOBREVIN 1; TAU PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; BLOOD BRAIN BARRIER; CAENORHABDITIS ELEGANS; CELL STRUCTURE; GENE MUTATION; IMMUNOHISTOCHEMISTRY; MITOCHONDRION; MOTONEURON; NERVE FIBER TRANSPORT; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; PHENOTYPE; PRESYNAPTIC NERVE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEOTOXICITY; TAU AGGREGATION INHIBITION; TAUOPATHY; TOXICITY; TRANSGENIC ORGANISM;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; AXONAL TRANSPORT; BLOOD-BRAIN BARRIER; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; DISEASE MODELS, ANIMAL; HUMANS; HYDRAZINES; METHYLENE BLUE; MITOCHONDRIA; MOTOR NEURONS; MUTATION; NEURONS; NEUROPROTECTIVE AGENTS; PHENOTYPE; PHOSPHORYLATION; PROTEIN STRUCTURE, TERTIARY; SENSORY RECEPTOR CELLS; TAU PROTEINS; TAUOPATHIES; THIAZOLES; VESICLE-ASSOCIATED MEMBRANE PROTEIN 1;

EID: 84865074623     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/dds190     Document Type: Article

References (90)

1. Ballatore, C., Lee, V.M.-Y. and Trojanowski, J.Q. (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat. Rev. Neurosci., 8, 663-672.
2. Congdon, E.E. and Duff, K.E. (2008) Is tau aggregation toxic or protective? J. Alzheimers Dis., 14, 453-457.
3. Iqbal, K., Wang, X., Blanchard, J., Liu, F., Gong, C.-X. and Grundke-Iqbal, I. (2010) Alzheimer's disease neurofibrillary degeneration: pivotal and multifactorial. Biochem. Soc. Trans., 38, 962-966.
4. Obulesu, M., Venu, R. and Somashekhar, R. (2011) Tau mediated neurodegeneration: an insight into Alzheimer's disease pathology. Neurochem. Res., 36, 1329-1335.
5. Reiniger, L., Lukic, A., Linehan, J., Rudge, P., Collinge, J., Mead, S. and Brandner, S. (2011) Tau, prions and Abeta: the triad of neurodegeneration. Acta Neuropathol., 121, 5-20.
6. Morris, M., Maeda, S., Vossel, K. and Mucke, L. (2011) The many faces of Tau. Neuron, 70, 410-426.
7. Spires-Jones, T.L., Kopeikina, K.J., Koffie, R.M., de Calignon, A. and Hyman, B.T. (2011) Are tangles as toxic as they look? J. Mol. Neurosci., 45, 438-444.
8. Caughey, B. and Lansbury, P.T. (2003) Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu. Rev. Neurosci., 26, 267-298.
9. Uversky, V.N. (2010) Mysterious oligomerization of the amyloidogenic proteins. FEBS J., 277, 2940-2953.
10. Mocanu, M.-M., Nissen, A., Eckermann, K., Khlistunova, I., Biernat, J., Drexler, D., Petrova, O., Schonig, K., Bujard, H., Mandelkow, E. et al. (2008) The potential for beta-structure in the repeat domain of Tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous Tau in inducible mouse models of tauopathy. J. Neurosci., 28, 737-748.
11. Eckermann, K., Mocanu, M.-M., Khlistunova, I., Biernat, J., Nissen, A., Hofmann, A., Schönig, K., Bujard, H., Haemisch, A., Mandelkow, E. et al. (2007) The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy. J. Biol. Chem., 282, 31755-31765.
12. Khlistunova, I., Biernat, J., Wang, Y., Pickhardt, M., von Bergen, M., Gazova, Z., Mandelkow, E. and Mandelkow, E.-M. (2006) Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J. Biol. Chem., 281, 1205-1214.
13. Sydow, A., Van der Jeugd, A., Zheng, F., Ahmed, T., Balschun, D., Petrova, O., Drexler, D., Zhou, L., Rune, G., Mandelkow, E. et al. (2011) Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic tau mutant. J. Neurosci., 31, 2511-2525.
14. Santacruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E. et al. (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science, 309, 476-481.
15. von Bergen, M., Barghorn, S., Li, L., Marx, A., Biernat, J., Mandelkow, E.M. and Mandelkow, E. (2001) Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J. Biol. Chem., 276, 48165-48174.
16. Wang, Y.P., Biernat, J., Pickhardt, M., Mandelkow, E. and Mandelkow, E.-M. (2007) Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model. Proc. Natl Acad. Sci. USA, 104, 10252-10257.
17. Wang, Y., Martinez-Vicente, M., Kruger, U., Kaushik, S., Wong, E., Mandelkow, E.M., Cuervo, A.M. and Mandelkow, E. (2009) Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum. Mol. Genet., 18, 4153-4170.
18. Artal-Sanz, M., de Jong, L. and Tavernarakis, N. (2006) Caenorhabditis elegans: a versatile platform for drug discovery. Biotechnol. J., 1, 1405-1418.
19. Voisine, C., Varma, H., Walker, N., Bates, E.A., Stockwell, B.R. and Hart, A.C. (2007) Identification of potential therapeutic drugs for huntington's disease using Caenorhabditis elegans. PLoS ONE, 2, e504.
20. Giacomotto, J. and Segalat, L. (2010) High-throughput screening and small animal models, where are we? Br. J. Pharmacol., 160, 204-216.
21. Braungart, E., Gerlach, M., Riederer, P., Baumeister, R. and Hoener, M.C. (2004) Caenorhabditis elegans MPP+ model of Parkinson's disease for high-throughput drug screenings. Neurodegener. Dis., 1, 175-183.
22. Kraemer, B.C. and Schellenberg, G.D. (2007) SUT-1 enables tau-induced neurotoxicity in C. elegans. Hum. Mol. Genet., 16, 1959-1971.
23. Kraemer, B.C., Burgess, J.K., Chen, J.H., Thomas, J.H. and Schellenberg, G.D. (2006) Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans. Hum. Mol. Genet., 15, 1483-1496.
24. Kraemer, B.C., Zhang, B., Leverenz, J.B., Thomas, J.H., Trojanowski, J.Q. and Schellenberg, G.D. (2003) Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc. Natl Acad. Sci. USA, 100, 9980-9985.
25. Brandt, R., Gergou, A., Wacker, I., Fath, T. and Hutter, H. (2009) A Caenorhabditis elegans model of tau hyperphosphorylation: induction of developmental defects by transgenic overexpression of Alzheimer's disease-like modified tau. Neurobiol. Aging, 30, 22-33.
26. Guthrie, C.R., Schellenberg, G.D. and Kraemer, B.C. (2009) SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans. Hum. Mol. Genet., 18, 1825-1838.
27. Miyasaka, T., Ding, Z., Gengyo-Ando, K., Oue, M., Yamaguchi, H., Mitani, S. and Ihara, Y. (2005) Progressive neurodegeneration in C. elegans model of tauopathy. Neurobiol. Dis., 20, 372-383.
28. Wheeler, J.M., Guthrie, C.R. and Kraemer, B.C. (2010) The role of MSUT-2 in tau neurotoxicity: a target for neuroprotection in tauopathy? Biochem. Soc. Trans., 38, 973-976.
29. Goedert, M., Baur, C.P., Ahringer, J., Jakes, R., Hasegawa, M., Spillantini, M.G., Smith, M.J. and Hill, F. (1996) PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J. Cell Sci., 109, 2661-2672.
30. Gordon, P., Hingula, L., Krasny, M.L., Swienckowski, J.L., Pokrywka, N.J. and Raley-Susman, K.M. (2008) The invertebrate microtubuleassociated protein PTL-1 functions in mechanosensation and development in Caenorhabditis elegans. Dev. Genes Evol., 218, 541-551.
31. Taniguchi, S., Suzuki, N., Masuda, M., Hisanaga, S., Iwatsubo, T., Goedert, M. and Hasegawa, M. (2005) Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. J. Biol. Chem., 280, 7614-7623.
32. Wischik, C.M., Edwards, P.C., Lai, R.Y., Roth, M. and Harrington, C.R. (1996) Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc. Natl Acad. Sci. USA, 93, 11213-11218.
33. Ballatore, C., Brunden, K.R., Piscitelli, F., James, M.J., Crowe, A., Yao, Y., Hyde, E., Trojanowski, J.Q., Lee, V.M. and Smith, A.B. III (2010) Discovery of brain-penetrant, orally bioavailable aminothienopyridazine inhibitors of tau aggregation. J. Med. Chem., 53, 3739-3747.
34. Link, C.D. (1995) Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc. Natl Acad. Sci. USA, 92, 9368-9372.
35. Minniti, A.N., Rebolledo, D.L., Grez, P.M., Fadic, R., Aldunate, R., Volitakis, I., Cherny, R.A., Opazo, C., Masters, C., Bush, A.I. et al. (2009) Intracellular amyloid formation in muscle cells of Abeta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification. Mol. Neurodegener., 4, 2.
36. Iqbal, K., Alonso Adel, C., Chen, S., Chohan, M.O., El-Akkad, E., Gong, C.X., Khatoon, S., Li, B., Liu, F., Rahman, A. et al. (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta, 1739, 198-210.
37. Kosik, K.S. and Shimura, H. (2005) Phosphorylated tau and the neurodegenerative foldopathies. Biochim. Biophys. Acta, 1739, 298-310.
38. Augustinack, J.C., Schneider, A., Mandelkow, E.M. and Hyman, B.T. (2002) Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol., 103, 26-35.
39. Paquet, D., Bhat, R., Sydow, A., Mandelkow, E.M., Berg, S., Hellberg, S., Falting, J., Distel, M., Koster, R.W., Schmid, B. et al. (2009) A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J. Clin. Invest., 119, 1382-1395.
40. Kosmidis, S., Grammenoudi, S., Papanikolopoulou, K. and Skoulakis, E.M. (2010) Differential effects of Tau on the integrity and function of neurons essential for learning in Drosophila. J. Neurosci., 30, 464-477.
41. Papanikolopoulou, K., Kosmidis, S., Grammenoudi, S. and Skoulakis, E.M. (2010) Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction. Biochem. Soc. Trans., 38, 981-987.
42. Ambegaokar, S.S. and Jackson, G.R. (2011) Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation. Hum. Mol. Genet., 20, 4947-4977.
43. Talmat-Amar, Y., Arribat, Y., Redt-Clouet, C., Feuillette, S., Bouge, A.L., Lecourtois, M. and Parmentier, M.L. (2011) Important neuronal toxicity of microtubule-bound Tau in vivo in Drosophila. Hum. Mol. Genet., 20, 3738-3745.
44. Samuelson, A.V., Klimczak, R.R., Thompson, D.B., Carr, C.E. and Ruvkun, G. (2007) Identification of Caenorhabditis elegans genes regulating longevity using enhanced RNAi-sensitive strains. Cold Spring Harb. Symp. Quant. Biol., 72, 489-497.
45. Lundquist, E.A., Reddien, P.W., Hartwieg, E., Horvitz, H.R. and Bargmann, C.I. (2001) Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis. Development, 128, 4475-4488.
46. Schultheis, C., Brauner, M., Liewald, J.F. and Gottschalk, A. (2011) Optogenetic analysis of GABAB receptor signaling in Caenorhabditis elegans motor neurons. J. Neurophysiol., 106, 817-827.
47. Weimer, R.M., Richmond, J.E., Davis, W.S., Hadwiger, G., Nonet, M.L. and Jorgensen, E.M. (2003) Defects in synaptic vesicle docking in unc-18 mutants. Nat. Neurosci., 6, 1023-1030.
48. Nonet, M.L. (1999) Visualization of synaptic specializations in live C. elegans with synaptic vesicle protein-GFP fusions. J. Neurosci. Methods, 89, 33-40.
49. Jin, Y. (2002) Synaptogenesis: insights from worm and fly. Curr. Opin. Neurobiol., 12, 71-79.
50. Mahoney, T.R., Luo, S. and Nonet, M.L. (2006) Analysis of synaptic transmission in Caenorhabditis elegans using an aldicarb-sensitivity assay. Nat. Protoc., 1, 1772-1777.
51. Lasagna-Reeves, C.A., Castillo-Carranza, D.L., Sengupta, U., Clos, A.L., Jackson, G.R. and Kayed, R. (2011) Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice. Mol. Neurodegener., 6, 39.
52. Schon, E.A. and Przedborski, S. (2011) Mitochondria: the next (neurode)generation. Neuron, 70, 1033-1053.
53. Thies, E. and Mandelkow, E.M. (2007) Missorting of tau in neurons causes degeneration of synapses that can be rescued by the kinase MARK2/Par-1. J. Neurosci., 27, 2896-2907.
54. Klassen, M.P., Wu, Y.E., Maeder, C.I., Nakae, I., Cueva, J.G., Lehrman, E.K., Tada, M., Gengyo-Ando, K., Wang, G.J., Goodman, M. et al. (2010) An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation. Neuron, 66, 710-723.
55. Deiana, S., Harrington, C.R., Wischik, C.M. and Riedel, G. (2009) Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine. Psychopharmacology, 202, 53-65.
56. Schirmer, R.H., Adler, H., Pickhardt, M. and Mandelkow, E. (2011) 'Lest we forget you - methylene blue... 'Neurobiol. Aging, 32, 2325.e7-2325.e16.
57. Pickhardt, M., Larbig, G., Khlistunova, I., Coksezen, A., Meyer, B., Mandelkow, E.-M., Schmidt, B. and Mandelkow, E. (2007) Phenylthiazolyl-hydrazide and its derivatives are potent inhibitors of tau aggregation and toxicity in vitro and in cells. Biochemistry, 46, 10016-10023.
58. Earls, L.R., Hacker, M.L., Watson, J.D. and Miller, D.M. III (2010) Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration. Proc. Natl Acad. Sci. USA, 107, 14460-14465.
59. Ben-Zvi, A., Miller, E.A. and Morimoto, R.I. (2009) Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc. Natl Acad. Sci. USA, 106, 14914-14919.
60. David, D.C., Ollikainen, N., Trinidad, J.C., Cary, M.P., Burlingame, A.L. and Kenyon, C. (2010) Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol., 8, e1000450.
61. Dillin, A. and Cohen, E. (2011) Ageing and protein aggregation-mediated disorders: from invertebrates to mammals. Philos. Trans. R. Soc. B Biol. Sci., 366, 94-98.
62. Cohen, E. and Dillin, A. (2008) The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat. Rev. Neurosci., 9, 759-767.
63. De Vos, K., Grierson, A., Ackerley, S. and Miller, C. (2008) Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci., 31, 151-173.
64. Ittner, L.M., Fath, T., Ke, Y.D., Bi, M., van Eersel, J., Li, K.M., Gunning, P. and Götz, J. (2008) Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia. Proc. Natl Acad. Sci. USA, 105, 15997-16002.
65. Roy, S., Zhang, B., Lee, V.M.-Y. and Trojanowski, J.Q. (2005) Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol., 109, 5-13.
66. Stamer, K., Vogel, R., Thies, E., Mandelkow, E. and Mandelkow, E.M. (2002) Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J. Cell Biol., 156, 1051-1063.
67. Brown, A. (2003) Axonal transport of membranous and nonmembranous cargoes: a unified perspective. J. Cell Biol., 160, 817-821.
68. Mandelkow, E.M., Thies, E., Trinczek, B., Biernat, J. and Mandelkow, E. (2004) MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. J. Cell Biol., 167, 99-110.
69. Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M.P., Klein, W.L., Link, C.D. and Luo, Y. (2006) Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci., 26, 13102-13113.
70. Diomede, L., Cassata, G., Fiordaliso, F., Salio, M., Ami, D., Natalello, A., Doglia, S.M., De Luigi, A. and Salmona, M. (2010) Tetracycline and its analogues protect Caenorhabditis elegans from beta amyloid-induced toxicity by targeting oligomers. Neurobiol. Dis., 40, 424-431.
71. Silva, M.C., Fox, S., Beam, M., Thakkar, H., Amaral, M.D. and Morimoto, R.I. (2011) A genetic screening strategy identifies novel regulators of the proteostasis network. PLoS Genet., 7, e1002438.
72. Sleigh, J.N., Buckingham, S.D., Esmaeili, B., Viswanathan, M., Cuppen, E., Westlund, B.M. and Sattelle, D.B. (2011) A novel Caenorhabditis elegans allele, smn-1(cb131), mimicking a mild form of spinal muscular atrophy, provides a convenient drug screening platform highlighting new and pre-approved compounds. Hum. Mol. Genet., 20, 245-260.
73. Medina, D.X., Caccamo, A. and Oddo, S. (2011) Methylene blue reduces abeta levels and rescues early cognitive deficit by increasing proteasome activity. Brain Pathol., 21, 140-149.
74. Bulic, B., Pickhardt, M., Khlistunova, I., Biernat, J., Mandelkow, E.-M., Mandelkow, E. and Waldmann, H. (2007) Rhodanine-based tau aggregation inhibitors in cell models of tauopathy. Angew. Chem. Int. Ed. Engl., 46, 9215-9219.
75. Bulic, B., Pickhardt, M., Mandelkow, E.-M. and Mandelkow, E. (2010) Tau protein and tau aggregation inhibitors. Neuropharmacology, 59, 276-289.
76. Burns, A.R., Wallace, I.M., Wildenhain, J., Tyers, M., Giaever, G., Bader, G.D., Nislow, C., Cutler, S.R. and Roy, P.J. (2010) A predictive model for drug bioaccumulation and bioactivity in Caenorhabditis elegans. Nat. Chem. Biol., 6, 549-557.
77. Cho, J.E. and Kim, J.R. (2011) Recent approaches targeting beta-amyloid for therapeutic intervention of Alzheimer's disease. Recent Patents CNS Drug Discov., 6, 222-233.
78. Schneider, A. and Mandelkow, E. (2008) Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics, 5, 443-457.
79. Voisine, C., Pedersen, J.S. and Morimoto, R.I. (2010) Chaperone networks: tipping the balance in protein folding diseases. Neurobiol. Dis., 40, 12-20.
80. Sirangelo, I. and Irace, G. (2010) Inhibition of aggregate formation as therapeutic target in protein misfolding diseases: effect of tetracycline and trehalose. Expert Opin. Ther. Targets, 14, 1311-1321.
81. Landau, M., Sawaya, M.R., Faull, K.F., Laganowsky, A., Jiang, L., Sievers, S.A., Liu, J., Barrio, J.R. and Eisenberg, D. (2011) Towards a pharmacophore for amyloid. PLoS Biol., 9, e1001080.
82. Sievers, S.A., Karanicolas, J., Chang, H.W., Zhao, A., Jiang, L., Zirafi, O., Stevens, J.T., Münch, J., Baker, D. and Eisenberg, D. (2011) Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature, 475, 96-100.
83. Alavez, S., Vantipalli, M.C., Zucker, D.J., Klang, I.M. and Lithgow, G.J. (2011) Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature, 472, 226-229.
84. Kayed, R., Head, E., Thompson, J.L., McIntire, T.M., Milton, S.C., Cotman, C.W. and Glabe, C.G. (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science, 300, 486-489.
85. Nyamsuren, O., Faggionato, D., Loch, W., Schulze, E. and Baumeister, R. (2007) A mutation in CHN-1/CHIP suppresses muscle degeneration in Caenorhabditis elegans. Dev. Biol., 312, 193-202.
86. Ishihara, T., Hong, M., Zhang, B., Nakagawa, Y., Lee, M.K., Trojanowski, J.Q. and Lee, V.M. (1999) Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron, 24, 751-762.
87. Sandoval, G.M., Duerr, J.S., Hodgkin, J., Rand, J.B. and Ruvkun, G. (2006) A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans. Nat. Neurosci., 9, 599-601.
88. Wasserman, S.M., Beverly, M., Bell, H.W. and Sengupta, P. (2011) Regulation of response properties and operating range of the AFD thermosensory neurons by cGMP signaling. Curr. Biol., 21, 353-362.
89. Gottschalk, A., Almedom, R.B., Schedletzky, T., Anderson, S.D., Yates, J.R. III and Schafer, W.R. (2005) Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans. EMBO J., 24, 2566-2578.
90. Wood, W.B. (1988) Determination of pattern and fate in early embryos of Caenorhabditis elegans. Dev. Biol., 5, 57-78.