Use of C. elegans as a model to study Alzheimer's disease and other neurodegenerative diseases

Frontiers in Genetics

Volumn 5, Issue JUL, 2014, Pages

  Alexander, Adanna G ^a   Marfil, Vanessa ^a   Li, Chris ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ADM 4 PROTEIN; AMYLOID PRECURSOR PROTEIN; AMYLOID PROTEIN; CAENORHABDITIS ELEGANS PROTEIN; GLP 1 PROTEIN; LEUCINE RICH REPEAT KINASE 2; LIN 12 PROTEIN; MEGALIN; MICRORNA; PARKIN; SUP 17 PROTEIN; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; APL 1 GENE; ARTICLE; CAENORHABDITIS ELEGANS; CELL TRANSPORT; CONNECTOME; DEGENERATIVE DISEASE; DISEASE MODEL; FRONTOTEMPORAL DEMENTIA; GENE; GENE CONTROL; GENE EXPRESSION; GENE FUNCTION; HUMAN; HUNTINGTON CHOREA; INTRACELLULAR TRANSPORT; LEARNING; MEMORY DISORDER; MOLECULAR PATHOLOGY; MULTIGENE FAMILY; NEUROFIBRILLARY TANGLE; NONHUMAN; PARKINSON DISEASE; PROTEIN DOMAIN; PROTEIN PROCESSING; SYNAPTIC TRANSMISSION; TOUCH;

EID: 84906267591     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2014.00279     Document Type: Article

References (311)

1. Adlard, P.A., Cherny, R.A., Finkelstein, D.I., Gautier, E., Robb, E., Cortes, M., Volitakis, I., Liu, X., Smith, J.P., Perez, K., Laughton, K., Li, Q.X., Charman, S.A., Nicolazzo, J.A., Wilkins, S., Deleva, K., Lynch, T., Kok, G., Ritchie, C.W., Tanzi, R.E., Cappai, R., Masters, C.L., Barnham, K.J., Bush, A.I. (2008). Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron 59, 43-55.
2. Aizawa, H., Emori, Y., Murofushi, H., Kawasaki, H., Sakai, H., Suzuki, K. (1990). Molecular cloning of a ubiquitously distributed microtubule-associated protein with Mr 190,000. J Biol Chem 265, 13849-13855.
3. Alonso, A., Zaidi, T., Novak, M., Grundke-Iqbal, I., Iqbal, K. (2001). Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc Natl Acad Sci U S A 98, 6923-6928.
4. Alonso, A.C., Grundke-Iqbal, I., Iqbal, K. (1996). Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 2, 783-787.
5. Alonso, A.D., Grundke-Iqbal, I., Barra, H.S., Iqbal, K. (1997). 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. Proc Natl Acad Sci U S A 94, 298-303.
6. Ambros, V., Horvitz, H.R. (1984). Heterochronic mutants of the nematode Caenorhabditis elegans. Science 226, 409-416.
7. Amos, L.A., Schlieper, D. (2005). Microtubules and maps. Adv Protein Chem 71, 257-298.
8. Arduengo, P.M., Appleberry, O.K., Chuang, P., L'hernault, S.W. (1998). The presenilin protein family member SPE-4 localizes to an ER/Golgi derived organelle and is required for proper cytoplasmic partitioning during Caenorhabditis elegans spermatogenesis. J Cell Sci 111 (Pt 24), 3645-3654.
9. Arimoto, M., Koushika, S.P., Choudhary, B.C., Li, C., Matsumoto, K., Hisamoto, N. (2011). The Caenorhabditis elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein. J Neurosci 31, 2216-2224.
10. Asahina, M., Ishihara, T., Jindra, M., Kohara, Y., Katsura, I., Hirose, S. (2000). The conserved nuclear receptor Ftz-F1 is required for embryogenesis, moulting and reproduction in Caenorhabditis elegans. Genes Cells 5, 711-723.
11. Ash, P.E., Zhang, Y.J., Roberts, C.M., Saldi, T., Hutter, H., Buratti, E., Petrucelli, L., Link, C.D. (2010). Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum Mol Genet 19, 3206-3218.
12. Bargmann, C.I., Hartwieg, E., Horvitz, H.R. (1993). Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74, 515-527.
13. Bargmann, C.I., Horvitz, H.R. (1991). Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron 7, 729-742.
14. Bates, E.A., Victor, M., Jones, A.K., Shi, Y., Hart, A.C. (2006). Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity. J Neurosci 26, 2830-2838.
15. Biernat, J., Gustke, N., Drewes, G., Mandelkow, E.M., Mandelkow, E. (1993). Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron 11, 153-163.
16. Bieschke, J., Cohen, E., Murray, A., Dillin, A., Kelly, J.W. (2009). A kinetic assessment of the C. elegans amyloid disaggregation activity enables uncoupling of disassembly and proteolysis. Protein Sci 18, 2231-2241.
17. Billingsley, M.L., Kincaid, R.L. (1997). Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem J 323 (Pt 3), 577-591.
18. Binder, L.I., Frankfurter, A., Rebhun, L.I. (1985). The distribution of tau in the mammalian central nervous system. J Cell Biol 101, 1371-1378.
19. Boccitto, M., Lamitina, T., Kalb, R.G. (2012). Daf-2 signaling modifies mutant SOD1 toxicity in C. elegans. PLoS One 7, e33494.
20. Borgonovo, B., Ouwendijk, J., Solimena, M. (2006). Biogenesis of secretory granules. Curr Opin Cell Biol 18, 365-370.
21. Borroni, B., Bonvicini, C., Alberici, A., Buratti, E., Agosti, C., Archetti, S., Papetti, A., Stuani, C., Di Luca, M., Gennarelli, M., Padovani, A. (2009). Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum Mutat 30, E974-983.
22. Bramblett, G.T., Goedert, M., Jakes, R., Merrick, S.E., Trojanowski, J.Q., Lee, V.M. (1993). Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron 10, 1089-1099.
23. Brandt, R., Gergou, A., Wacker, I., Fath, T., 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.
24. Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
25. Brignull, H.R., Moore, F.E., Tang, S.J., Morimoto, R.I. (2006). Polyglutamine proteins at the pathogenic threshold display neuron-specific aggregation in a pan-neuronal Caenorhabditis elegans model. J Neurosci 26, 7597-7606.
26. Brown, M.S., Goldstein, J.L. (1986). A receptor-mediated pathway for cholesterol homeostasis. Science 232, 34-47.
27. Bulinski, J.C., Borisy, G.G. (1980). Microtubule-associated proteins from cultured HeLa cells. Analysis of molecular properties and effects on microtubule polymerization. J Biol Chem 255, 11570-11576.
28. Büttner, S., Habernig, L., Broeskamp, F., Ruli, D., Vögtle, F.N., Vlachos, M., Macchi, F., Küttner, V., Carmona-Gutierrez, D., Eisenberg, T., Ring, J., Markaki, M., Taskin, A.A., Benke, S., Ruckenstuhl, C., Braun, R., Van Den Haute, C., Bammens, T., Van Der Perren, A., Fröhlich, K.U., Winderickx, J., Kroemer, G., Baekelandt, V., Tavernarakis, N., Kovacs, G.G., Dengjel, J., Meisinger, C., Sigrist, S.J., Madeo, F. (2013). Endonuclease G mediates a-synuclein cytotoxicity during Parkinson's disease. EMBO J 32, 3041-3054.
29. Cam, J.A., Bu, G. (2006). Modulation of beta-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family. Mol Neurodegener 1, 8.
30. Cao, P., Yuan, Y., Pehek, E.A., Moise, A.R., Huang, Y., Palczewski, K., Feng, Z. (2010). Alpha-synuclein disrupted dopamine homeostasis leads to dopaminergic neuron degeneration in Caenorhabditis elegans. PLoS One 5, e9312.
31. Carro, E., Spuch, C., Trejo, J.L., Antequera, D., Torres-Aleman, I. (2005). Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I. J Neurosci 25, 10884-10893.
32. Chalfie, M., Horvitz, H.R., Sulston, J.E. (1981). Mutations that lead to reiterations in the cell lineages of C. elegans. Cell 24, 59-69.
33. Chalfie, M., Sulston, J. (1981). Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol 82, 358-370.
34. Chalfie, M., Sulston, J.E., White, J.G., Southgate, E., Thomson, J.N., Brenner, S. (1985). The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci 5, 956-964.
35. Chapin, S.J., Bulinski, J.C. (1991). Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau. J Cell Sci 98 (Pt 1), 27-36.
36. Chartier-Harlin, M.C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J. (1991). Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 353, 844-846.
37. Chen, J., Kanai, Y., Cowan, N.J., Hirokawa, N. (1992). Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons. Nature 360, 674-677.
38. Chew, Y.L., Fan, X., Götz, J., Nicholas, H.R. (2013). PTL-1 regulates neuronal integrity and lifespan in C. elegans. J Cell Sci 126, 2079-2091.
39. Cohen, E., Bieschke, J., Perciavalle, R.M., Kelly, J.W., Dillin, A. (2006). Opposing activities protect against age-onset proteotoxicity. Science 313, 1604-1610.
40. Colbert, H.A., Bargmann, C.I. (1995). Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans. Neuron 14, 803-812.
41. Consortium, C.E.S. (1998). Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012-2018.
42. Conway, K.A., Harper, J.D., Lansbury, P.T. (2000a). Fibrils formed in vitro from alpha894 synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry 39, 2552-2563.
43. Conway, K.A., Lee, S.J., Rochet, J.C., Ding, T.T., Harper, J.D., Williamson, R.E., Lansbury, P.T. (2000b). Accelerated oligomerization by Parkinson's disease linked alpha-synuclein mutants. Ann N Y Acad Sci 920, 42-45.
44. Conway, K.A., Lee, S.J., Rochet, J.C., Ding, T.T., Williamson, R.E., Lansbury, P.T. (2000c). Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci U S A 97, 571-576.
45. Cruts, M., Theuns, J., Van Broeckhoven, C. (2012). Locus-specific mutation databases for neurodegenerative brain diseases. Hum Mutat 33, 1340-1344.
46. Cui, S., Verroust, P.J., Moestrup, S.K., Christensen, E.I. (1996). Megalin/gp330 mediates uptake of albumin in renal proximal tubule. Am J Physiol 271, F900-907.
47. Daigle, I., Li, C. (1993). apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Proc Natl Acad Sci U S A 90, 12045-12049.
48. Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., Larue, B., Hu, H.W., Spijkers, P., Guo, H., Song, X., Lenting, P.J., Van Nostrand, W.E., Zlokovic, B.V. (2004). LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 43, 333-344.
49. Dejesus-Hernandez, M., Mackenzie, I.R., Boeve, B.F., Boxer, A.L., Baker, M., Rutherford, N.J., Nicholson, A.M., Finch, N.A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G.Y., Karydas, A., Seeley, W.W., Josephs, K.A., Coppola, G., Geschwind, D.H., Wszolek, Z.K., Feldman, H., Knopman, D.S., Petersen, R.C., Miller, B.L., Dickson, D.W., Boylan, K.B., Graff-Radford, N.R., Rademakers, R. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245-256.
50. Dragunow, M., Faull, R.L., Lawlor, P., Beilharz, E.J., Singleton, K., Walker, E.B., Mee, E. (1995). In situ evidence for DNA fragmentation in Huntington's disease striatum and Alzheimer's disease temporal lobes. Neuroreport 6, 1053-1057.
51. Duarte, A., Hirashima, M., Benedito, R., Trindade, A., Diniz, P., Bekman, E., Costa, L., Henrique, D., Rossant, J. (2004). Dosage-sensitive requirement for mouse Dll4 in artery development. Genes Dev 18, 2474-2478.
52. Duilio, A., Faraonio, R., Minopoli, G., Zambrano, N., Russo, T. (1998). Fe65L2: a new member of the Fe65 protein family interacting with the intracellular domain of the Alzheimer's beta-amyloid precursor protein. Biochem J 330 (Pt 1), 513-519.
53. Dumas, K.J., Guo, C., Wang, X., Burkhart, K.B., Adams, E.J., Alam, H., Hu, P.J. (2010). Functional divergence of dafachronic acid pathways in the control of C. elegans development and lifespan. Dev Biol 340, 605-612.
54. Eimer, S., Miller, K.G. (2009). Impaired dense core vesicle maturation in Caenorhabditis elegans mutants lacking Rab2. J Cell Biol 186, 881-895.
55. Estevez, A.O., Morgan, K.L., Szewczyk, N.J., Gems, D., Estevez, M. (2014). The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans. Neurotoxicology 41C, 28-43.
56. Estevez, A.O., Mueller, C.L., Morgan, K.L., Szewczyk, N.J., Teece, L., Miranda-Vizuete, A., Estevez, M. (2012). Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans. Neurotoxicology 33, 1021-1032.
57. Ewald, C.Y., Cheng, R., Tolen, L., Shah, V., Gillani, A., Nasrin, A., Li, C. (2012a). Pan943 neuronal expression of APL-1, an APP-related protein, disrupts olfactory, gustatory, and touch plasticity in Caenorhabditis elegans. J Neurosci 32, 10156-10169.
58. Ewald, C.Y., Raps, D.A., Li, C. (2012b). APL-1, the Alzheimer's Amyloid precursor protein in Caenorhabditis elegans, modulates multiple metabolic pathways throughout development. Genetics 191, 493-507.
59. Faber, P.W., Alter, J.R., Macdonald, M.E., Hart, A.C. (1999). Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci U S A 96, 179-184.
60. Faber, P.W., Voisine, C., King, D.C., Bates, E.A., Hart, A.C. (2002). Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity. Proc Natl Acad Sci U S A 99, 17131-17136.
61. Fahn, S., Sulzer, D. (2004). Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 1, 139-154.
62. Farg, M.A., Sundaramoorthy, V., Sultana, J.M., Yang, S., Atkinson, R.A., Levina, V., Halloran, M.A., Gleeson, P.A., Blair, I.P., Soo, K.Y., King, A.E., Atkin, J.D. (2014). C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum Mol Genet.
63. Farrer, L.A., Conneally, P.M. (1985). A genetic model for age at onset in Huntington disease. Am J Hum Genet 37, 350-357.
64. Fatouros, C., Pir, G.J., Biernat, J., Koushika, S.P., Mandelkow, E., Mandelkow, E.M., Schmidt, E., Baumeister, R. (2012). Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity. Hum Mol Genet 21, 3587-3603.
65. Feijoo, C., Campbell, D.G., Jakes, R., Goedert, M., Cuenda, A. (2005). Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J Cell Sci 118, 397-408.
66. Fonte, V., Kapulkin, W.J., Kapulkin, V., Taft, A., Fluet, A., Friedman, D., Link, C.D. (2002). Interaction of intracellular beta amyloid peptide with chaperone proteins. Proc Natl Acad Sci U S A 99, 9439-9444.
67. Fonte, V., Kipp, D.R., Yerg, J., Merin, D., Forrestal, M., Wagner, E., Roberts, C.M., Link, C.D. (2008). Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J Biol Chem 283, 784-791.
68. Francis, R., Mcgrath, G., Zhang, J., Ruddy, D.A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M.C., Parks, A.L., Xu, W., Li, J., Gurney, M., Myers, R.L., Himes, C.S., Hiebsch, R., Ruble, C., Nye, J.S., Curtis, D. (2002). aph-1 and pen-2 are required for and presenilin protein accumulation. Dev Cell 3, 85-97.
69. Frøkjaer-Jensen, C., Davis, M.W., Hopkins, C.E., Newman, B.J., Thummel, J.M., Olesen, S.P., Grunnet, M., Jorgensen, E.M. (2008). Single-copy insertion of transgenes in Caenorhabditis elegans. Nat Genet 40, 1375-1383.
70. Gale, N.W., Dominguez, M.G., Noguera, I., Pan, L., Hughes, V., Valenzuela, D.M., Murphy, A.J., Adams, N.C., Lin, H.C., Holash, J., Thurston, G., Yancopoulos, G.D. (2004). Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc Natl Acad Sci U S A 101, 15949-15954.
71. Gasparini, L., Gouras, G.K., Wang, R., Gross, R.S., Beal, M.F., Greengard, P., Xu, H. (2001). Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 21, 2561-2570.
72. Gems, D., Sutton, A.J., Sundermeyer, M.L., Albert, P.S., King, K.V., Edgley, M.L., Larsen, P.L., Riddle, D.L. (1998). Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150, 129-155.
73. Gerisch, B., Weitzel, C., Kober-Eisermann, C., Rottiers, V., Antebi, A. (2001). A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev Cell 1, 841-851.
74. Gidalevitz, T., Krupinski, T., Garcia, S., Morimoto, R.I. (2009). Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. PLoS Genet 5, e1000399.
75. Gissendanner, C.R., Sluder, A.E. (2000). nhr-25, the Caenorhabditis elegans ortholog of ftz1002 f1, is required for epidermal and somatic gonad development. Dev Biol 221, 259-272.
76. Gitcho, M.A., Baloh, R.H., Chakraverty, S., Mayo, K., Norton, J.B., Levitch, D., Hatanpaa, K.J., White, C.L., Bigio, E.H., Caselli, R., Baker, M., Al-Lozi, M.T., Morris, J.C., Pestronk, A., Rademakers, R., Goate, A.M., Cairns, N.J. (2008). TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63, 535-538.
77. Glenner, G.G., Wong, C.W. (1984). Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122, 1131-1135.
78. Goate, A., Chartier-Harlin, M.C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704-706.
79. Goedert, M., Baur, C.P., Ahringer, J., Jakes, R., Hasegawa, M., Spillantini, M.G., Smith, M.J., Hill, F. (1996). PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J Cell Sci 109 (Pt 11), 2661-2672.
80. Goedert, M., Cohen, E.S., Jakes, R., Cohen, P. (1992a). p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease [corrected]. FEBS Lett 312, 95-99.
81. Goedert, M., Spillantini, M.G., Cairns, N.J., Crowther, R.A. (1992b). Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8, 159-168.
82. Goedert, M., Spillantini, M.G., Jakes, R., Rutherford, D., Crowther, R.A. (1989a). Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 3, 519-526.
83. Goedert, M., Spillantini, M.G., Potier, M.C., Ulrich, J., Crowther, R.A. (1989b). 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, 393-399.
84. Goedert, M., Wischik, C.M., Crowther, R.A., Walker, J.E., Klug, A. (1988). Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci U S A 85, 4051-4055.
85. Goldberg, Y.P., Kalchman, M.A., Metzler, M., Nasir, J., Zeisler, J., Graham, R., Koide, H.B., O'kusky, J., Sharp, A.H., Ross, C.A., Jirik, F., Hayden, M.R. (1996). Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. Hum Mol Genet 5, 177-185.
86. Gordon, P., Hingula, L., Krasny, M.L., Swienckowski, J.L., Pokrywka, N.J., Raley-Susman, K.M. (2008). The invertebrate microtubule-associated protein PTL-1 functions in mechanosensation and development in Caenorhabditis elegans. Dev Genes Evol 218, 541-551.
87. Gorevic, P.D., Goñi, F., Pons-Estel, B., Alvarez, F., Peress, N.S., Frangione, B. (1986). Isolation and partial characterization of neurofibrillary tangles and amyloid plaque core in Alzheimer's disease: immunohistological studies. J Neuropathol Exp Neurol 45, 647-664.
88. Goutte, C., Hepler, W., Mickey, K.M., Priess, J.R. (2000). aph-2 encodes a novel extracellular protein required for GLP-1-mediated signaling. Development 127, 2481-2492.
89. Goutte, C., Tsunozaki, M., Hale, V.A., Priess, J.R. (2002). APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. Proc Natl Acad Sci U S A 99, 775-779.
90. Greenwald, I.S., Sternberg, P.W., Horvitz, H.R. (1983). The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell 34, 435-444.
91. Gu, Y., Misonou, H., Sato, T., Dohmae, N., Takio, K., Ihara, Y. (2001). Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch. J Biol Chem 276, 35235-35238.
92. Gusella, J.F., Macdonald, M.E. (1995). Huntington's disease: CAG genetics expands neurobiology. Curr Opin Neurobiol 5, 656-662.
93. Guthrie, C.R., Greenup, L., Leverenz, J.B., Kraemer, B.C. (2011). MSUT2 is a determinant of susceptibility to tau neurotoxicity. Hum Mol Genet 20, 1989-1999.
94. Guthrie, C.R., Schellenberg, G.D., Kraemer, B.C. (2009). SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans. Hum Mol Genet 18, 1825-1838.
95. Guénette, S.Y., Chen, J., Jondro, P.D., Tanzi, R.E. (1996). Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein. Proc Natl Acad Sci U S A 93, 10832-10837.
96. Haass, C., Hung, A.Y., Selkoe, D.J., Teplow, D.B. (1994a). Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid beta1067 protein precursor. J Biol Chem 269, 17741-17748.
97. Haass, C., Koo, E.H., Mellon, A., Hung, A.Y., Selkoe, D.J. (1992). Targeting of cell-surface 1069 beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing 1070 fragments. Nature 357, 500-503.
98. Haass, C., Koo, E.H., Teplow, D.B., Selkoe, D.J. (1994b). Polarized secretion of beta1072 amyloid precursor protein and amyloid beta-peptide in MDCK cells. Proc Natl Acad Sci U S A 91, 1564-1568.
99. Hamamichi, S., Rivas, R.N., Knight, A.L., Cao, S., Caldwell, K.A., Caldwell, G.A. (2008). Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc Natl Acad Sci U S A 105, 728-733.
100. Hamos, J.E., Oblas, B., Pulaski-Salo, D., Welch, W.J., Bole, D.G., Drachman, D.A. (1991). Expression of heat shock proteins in Alzheimer's disease. Neurology 41, 345-350.
101. Han, S.M., El Oussini, H., Scekic-Zahirovic, J., Vibbert, J., Cottee, P., Prasain, J.K., Bellen, H.J., Dupuis, L., Miller, M.A. (2013). VAPB/ALS8 MSP ligands regulate striated muscle energy metabolism critical for adult survival in caenorhabditis elegans. PLoS Genet 9, e1003738.
102. Harada, A., Oguchi, K., Okabe, S., Kuno, J., Terada, S., Ohshima, T., Sato-Yoshitake, R., Takei, Y., Noda, T., Hirokawa, N. (1994). Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 369, 488-491.
103. Hardiman, O., Van Den Berg, L.H., Kiernan, M.C. (2011). Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol 7, 639-649.
104. Hardy, J. (2010). Genetic analysis of pathways to Parkinson disease. Neuron 68, 201-206.
105. Hayes, G.D., Frand, A.R., Ruvkun, G. (2006). The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25. Development 133, 4631-4641.
106. Heber, S., Herms, J., Gajic, V., Hainfellner, J., Aguzzi, A., Rülicke, T., Von Kretzschmar, H., Von Koch, C., Sisodia, S., Tremml, P., Lipp, H.P., Wolfer, D.P., Müller, U. (2000). Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci 20, 7951-7963.
107. Henderson, S.T., Johnson, T.E. (2001). daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11, 1975-1980.
108. Hermo, L., Lustig, M., Lefrancois, S., Argraves, W.S., Morales, C.R. (1999). Expression and regulation of LRP-2/megalin in epithelial cells lining the efferent ducts and epididymis during postnatal development. Mol Reprod Dev 53, 282-293.
109. Herms, J., Anliker, B., Heber, S., Ring, S., Fuhrmann, M., Kretzschmar, H., Sisodia, S., Müller, U. (2004). Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. EMBO J 23, 4106-4115.
110. Herz, J., Clouthier, D.E., Hammer, R.E. (1992). LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Cell 71, 411-421.
111. Hieb, W.F., Rothstein, M. (1968). Sterol requirement for reproduction of a free-living nematode. Science 160, 778-780.
112. Holcomb, L.A., Gordon, M.N., Jantzen, P., Hsiao, K., Duff, K., Morgan, D. (1999). Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav Genet 29, 177-185.
113. Hornsten, A., Lieberthal, J., Fadia, S., Malins, R., Ha, L., Xu, Daigle, I., Markowitz, M., O'connor, G., Plasterk, R., Li, C. (2007). APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability. Proc Natl Acad Sci U S A 104, 1971-1976.
114. Hsiao, K.K., Borchelt, D.R., Olson, K., Johannsdottir, R., Kitt, C., Yunis, W., Xu, S., Eckman, C., Younkin, S., Price, D. (1995). Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 15, 1203-1218.
115. Hsu, A.L., Murphy, C.T., Kenyon, C. (2003). Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300, 1142-1145.
116. Hughes, A.J., Ben-Shlomo, Y., Daniel, S.E., Lees, A.J. (1992). What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. Neurology 42, 1142-1146.
117. Hutton, M., Lendon, C.L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., Hackett, J., Adamson, J., Lincoln, S., Dickson, D., Davies, P., Petersen, R.C., Stevens, M., De Graaff, E., Wauters, E., Van Baren, J., Hillebrand, M., Joosse, M., Kwon, J.M., Nowotny, P., Che, L.K., Norton, J., Morris, J.C., Reed, L.A., Trojanowski, J., Basun, H., Lannfelt, L., Neystat, M., Fahn, S., Dark, F., Tannenberg, T., Dodd, P.R., Hayward, N., Kwok, J.B., Schofield, P.R., Andreadis, A., Snowden, J., Craufurd, D., Neary, D., Owen, F., Oostra, B.A., Hardy, J., Goate, A., Van Swieten, J., Mann, D., Lynch, T., Heutink, P. (1998). Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702-705.
118. International, A.D. (2014). Alzheimer disease international [Online]. Available: http://www.alz.co.uk/ [Accessed].
119. Jadiya, P., Khan, A., Sammi, S.R., Kaur, S., Mir, S.S., Nazir, A. (2011). Anti-Parkinsonian effects of Bacopa monnieri: insights from transgenic and pharmacological Caenorhabditis elegans models of Parkinson's disease. Biochem Biophys Res Commun 413, 605-610.
120. Jarriault, S., Greenwald, I. (2005). Evidence for functional redundancy between C. elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE. Dev Biol 287, 1-10.
121. Jia, K., Hart, A.C., Levine, B. (2007). Autophagy genes protect against disease caused by polyglutamine expansion proteins in Caenorhabditis elegans. Autophagy 3, 21-25.
122. Jonsson, T., Atwal, J.K., Steinberg, S., Snaedal, J., Jonsson, P.V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., Liu, Y., Lu, Y., Bhangale, T., Graham, R.R., Huttenlocher, J., Bjornsdottir, G., Andreassen, O.A., Jönsson, E.G., Palotie, A., Behrens, T.W., Magnusson, O.T., Kong, A., Thorsteinsdottir, U., Watts, R.J., Stefansson, K. (2012). A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488, 96-99.
123. Kabashi, E., Valdmanis, P.N., Dion, P., Spiegelman, D., Mcconkey, B.J., Vande Velde, C., Bouchard, J.P., Lacomblez, L., Pochigaeva, K., Salachas, F., Pradat, P.F., Camu, W., Meininger, V., Dupre, N., Rouleau, G.A. (2008). TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40, 572-574.
124. Kamel, F., Umbach, D.M., Bedlack, R.S., Richards, M., Watson, M., Alavanja, M.C., Blair, A., Hoppin, J.A., Schmidt, S., Sandler, D.P. (2012). Pesticide exposure and amyotrophic lateral sclerosis. Neurotoxicology 33, 457-462.
125. Kang, J., Lemaire, H.G., Unterbeck, A., Salbaum, J.M., Masters, C.L., Grzeschik, K.H., Multhaup, G., Beyreuther, K., Müller-Hill, B. (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736.
126. Kidd, M. (1964). ALZHEIMER'S DISEASE--AN ELECTRON MICROSCOPICAL STUDY. Brain 87, 307-320.
127. Kimberly, W.T., Lavoie, M.J., Ostaszewski, B.L., Ye, W., Wolfe, M.S., Selkoe, D.J. (2003). Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A 100, 6382-6387.
128. Kimura, K.D., Tissenbaum, H.A., Liu, Y., Ruvkun, G. (1997). daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946.
129. Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., Shimizu, N. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608.
130. Knauer, M.F., Orlando, R.A., Glabe, C.G. (1996). Cell surface APP751 forms complexes with protease nexin 2 ligands and is internalized via the low density lipoprotein receptor1174 related protein (LRP). Brain Res 740, 6-14.
131. Knops, J., Kosik, K.S., Lee, G., Pardee, J.D., Cohen-Gould, L., Mcconlogue, L. (1991). Overexpression of tau in a nonneuronal cell induces long cellular processes. J Cell Biol 114, 725-733.
132. Koo, E.H., Sisodia, S.S., Archer, D.R., Martin, L.J., Weidemann, A., Beyreuther, K., Fischer, P., Masters, C.L., Price, D.L. (1990). Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci U S A 87, 1561-1565.
133. Kounnas, M.Z., Moir, R.D., Rebeck, G.W., Bush, A.I., Argraves, W.S., Tanzi, R.E., Hyman, B.T., Strickland, D.K. (1995). LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Cell 82, 331-340.
134. Kraemer, B.C., Schellenberg, G.D. (2007). SUT-1 enables tau-induced neurotoxicity in C. elegans. Hum Mol Genet 16, 1959-1971.
135. Kraemer, B.C., Zhang, B., Leverenz, J.B., Thomas, J.H., Trojanowski, J.Q., Schellenberg, G.D. (2003). Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc Natl Acad Sci U S A 100, 9980-9985.
136. Krebs, L.T., Shutter, J.R., Tanigaki, K., Honjo, T., Stark, K.L., Gridley, T. (2004). Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 18, 2469-2473.
137. Krebs, L.T., Xue, Y., Norton, C.R., Shutter, J.R., Maguire, M., Sundberg, J.P., Gallahan, D., Closson, V., Kitajewski, J., Callahan, R., Smith, G.H., Stark, K.L., Gridley, T. (2000). Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 14, 1343-1352.
138. Krebs, L.T., Xue, Y., Norton, C.R., Sundberg, J.P., Beatus, P., Lendahl, U., Joutel, A., Gridley, T. (2003). Characterization of Notch3-deficient mice: normal embryonic development and absence of genetic interactions with a Notch1 mutation. Genesis 37, 139-143.
139. Krigman, M.R., Feldman, R.G., Bensch, K. (1965). ALZHEIMER'S PRESENILE DEMENTIA. A HISTOCHEMICAL AND ELECTRON MICROSCOPIC STUDY. Lab Invest 14, 381-396.
140. Kösel, S., Przuntek, H., Epplen, J.T., Schöls, L., Riess, O. (1998). Ala30Pro mutation in the gene encoding alpha1206 synuclein in Parkinson's disease. Nat Genet 18, 106-108.
141. Kuwahara, T., Koyama, A., Gengyo-Ando, K., Masuda, M., Kowa, H., Tsunoda, M., Mitani, S., Iwatsubo, T. (2006). Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. J Biol Chem 281, 334-340.
142. Kuwahara, T., Koyama, A., Koyama, S., Yoshina, S., Ren, C.H., Kato, T., Mitani, S., Iwatsubo, T. (2008). A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in alpha-synuclein transgenic C. elegans. Hum Mol Genet 17, 2997-3009.
143. L'hernault, S.W., Arduengo, P.M. (1992). Mutation of a putative sperm membrane protein in Caenorhabditis elegans prevents sperm differentiation but not its associated meiotic divisions. J Cell Biol 119, 55-68.
144. Lakowski, B., Eimer, S., Göbel, C., Böttcher, A., Wagler, B., Baumeister, R. (2003). Two suppressors of sel-12 encode C2H2 zinc-finger proteins that regulate presenilin transcription in Caenorhabditis elegans. Development 130, 2117-2128.
145. Lakso, M., Vartiainen, S., Moilanen, A.M., Sirviö, J., Thomas, J.H., Nass, R., Blakely, R.D., Wong, G. (2003). Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J Neurochem 86, 165-172.
146. Lambie, E.J., Kimble, J. (1991). Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. Development 112, 231-240.
147. Larsen, P.L., Albert, P.S., Riddle, D.L. (1995). Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139, 1567-1583.
148. Lee, B.H., Ashrafi, K. (2008). A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan. PLoS Genet 4, e1000213.
149. Lee, R.Y., Hench, J., Ruvkun, G. (2001). Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr Biol 11, 1950-1957.
150. Lee, V.M., Otvos, L., Carden, M.J., Hollosi, M., Dietzschold, B., Lazzarini, R.A. (1988). Identification of the major multiphosphorylation site in mammalian neurofilaments. Proc Natl Acad Sci U S A 85, 1998-2002.
151. Lejeune, F.X., Mesrob, L., Parmentier, F., Bicep, C., Vazquez-Manrique, R.P., Parker, J.A., Vert, J.P., Tourette, C., Neri, C. (2012). Large-scale functional RNAi screen in C. elegans identifies genes that regulate the dysfunction of mutant polyglutamine neurons. BMC Genomics 13, 91.
152. Levitan, D., Doyle, T.G., Brousseau, D., Lee, M.K., Thinakaran, G., Slunt, H.H., Sisodia, S.S., Greenwald, I. (1996). Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci U S A 93, 14940-14944.
153. Levitan, D., Greenwald, I. (1995). Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377, 351-354.
154. Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D.M., Oshima, J., Pettingell, W.H., Yu, C.E., Jondro, P.D., Schmidt, S.D., Wang, K. (1995). Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269, 973-977.
155. Lewis, S.A., Wang, D.H., Cowan, N.J. (1988). Microtubule-associated protein MAP2 shares a microtubule binding motif with tau protein. Science 242, 936-939.
156. Li, J., Li, T., Zhang, X., Tang, Y., Yang, J., and Le, W. (2014) Human superoxide dismutase 1 overexpression in motor neurons of Caenorhabditis elegans causes axon guidance defect and neurodegeneration. Neurobiol Aging 35, 837-846.
157. Li, L.Y., Luo, X., Wang, X. (2001). Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412, 95-99.
158. Li, T., Ma, G., Cai, H., Price, D.L., Wong, P.C. (2003). Nicastrin is required for assembly of presenilin/gamma-secretase complexes to mediate Notch signaling and for processing and trafficking of beta-amyloid precursor protein in mammals. J Neurosci 23, 3272-3277.
159. Li, X., Greenwald, I. (1996). Membrane topology of the C. elegans SEL-12 presenilin. Neuron 17, 1015-1021.
160. Li, X., Greenwald, I. (1997). HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling. Proc Natl Acad Sci U S A 94, 12204-12209.
161. Liang, J.J. (2000). Interaction between beta-amyloid and lens alphaB-crystallin. FEBS Lett 484, 98-101.
162. Lin, C.H., Tomioka, M., Pereira, S., Sellings, L., Iino, Y., Van Der Kooy, D. (2010). Insulin signaling plays a dual role in Caenorhabditis elegans memory acquisition and memory retrieval. J Neurosci 30, 8001-8011.
163. Lin, K., Dorman, J.B., Rodan, A., Kenyon, C. (1997). daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278, 1319-1322.
164. Lin, K., Hsin, H., Libina, N., Kenyon, C. (2001). Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28, 139-145.
165. Lindau, M., Almkvist, O., Kushi, J., Boone, K., Johansson, S.E., Wahlund, L.O., Cummings, J.L., Miller, B.L. (2000). First symptoms--frontotemporal dementia versus Alzheimer's disease. Dement Geriatr Cogn Disord 11, 286-293.
166. Lindwall, G., Cole, R.D. (1984). Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem 259, 5301-5305.
167. Link, C.D. (1995). Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci U S A 92, 9368-9372.
168. Link, C.D. (2006). C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer's disease. Exp Gerontol 41, 1007-1013.
169. Link, C.D., Johnson, C.J., Fonte, V., Paupard, M., Hall, D.H., Styren, S., Mathis, C.A., Klunk, W.E. (2001). Visualization of fibrillar amyloid deposits in living, transgenic Caenorhabditis elegans animals using the sensitive amyloid dye, X-34. Neurobiol Aging 22, 217-226.
170. Liu, Z., Hamamichi, S., Lee, B.D., Yang, D., Ray, A., Caldwell, G.A., Caldwell, K.A., Dawson, T.M., Smith, W.W., Dawson, V.L. (2011). Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models. Hum Mol Genet 20, 3933-3942.
171. Locke, C.J., Fox, S.A., Caldwell, G.A., Caldwell, K.A. (2008). Acetaminophen attenuates dopamine neuron degeneration in animal models of Parkinson's disease. Neurosci Lett 439, 129-133.
172. Lorent, K., Overbergh, L., Moechars, D., De Strooper, B., Van Leuven, F., Van Den Berghe, H. (1995). Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. Neuroscience 65, 1009-1025.
173. Lu, T., Aron, L., Zullo, J., Pan, Y., Kim, H., Chen, Y., Yang, T.H., Kim, H.M., Drake, D., Liu, X.S., Bennett, D.A., Colaiácovo, M.P., Yankner, B.A. (2014). REST and stress resistance in ageing and Alzheimer's disease. Nature 507, 448-454.
174. Luo, W.J., Wang, H., Li, H., Kim, B.S., Shah, S., Lee, H.J., Thinakaran, G., Kim, T.W., Yu, G., Xu, H. (2003). PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem 278, 7850-7854.
175. Luse, S.A., Smith, K.R. (1964). The ultrastructure of senile plaques. Am J Pathol 44, 553-563.
176. Mahley, R.W. (1988). Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240, 622-630.
177. Majounie, E., Abramzon, Y., Renton, A.E., Keller, M.F., Traynor, B.J., Singleton, A.B. (2012). Large C9orf72 repeat expansions are not a common cause of Parkinson's disease. Neurobiol Aging 33, 2527.e2521-2522.
178. Malek, A.M., Barchowsky, A., Bowser, R., Youk, A., Talbott, E.O. (2012). Pesticide exposure as a risk factor for amyotrophic lateral sclerosis: a meta-analysis of epidemiological studies: pesticide exposure as a risk factor for ALS. Environ Res 117, 112-119.
179. Mangahas, P.M., Yu, X., Miller, K.G., Zhou, Z. (2008). The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans. J Cell Biol 180, 357-373.
180. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W., Bates, G.P. (1996). Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506.
181. Martin, J.B., Gusella, J.F. (1986). Huntington's disease. Pathogenesis and management. N Engl J Med 315, 1267-1276.
182. Martindale, D., Hackam, A., Wieczorek, A., Ellerby, L., Wellington, C., Mccutcheon, K., Singaraja, R., Kazemi-Esfarjani, P., Devon, R., Kim, S.U., Bredesen, D.E., Tufaro, F., Hayden, M.R. (1998). Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet 18, 150-154.
183. Marvanova, M., Nichols, C.D. (2007). Identification of neuroprotective compounds of caenorhabditis elegans dopaminergic neurons against 6-OHDA. J Mol Neurosci 31, 127-137.
184. Masters, C.L., Simms, G., Weinman, N.A., Multhaup, G., Mcdonald, B.L., Beyreuther, K. (1985). Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82, 4245-4249.
185. Matus, A., Bernhardt, R., Hugh-Jones, T. (1981). High molecular weight microtubule1335 associated proteins are preferentially associated with dendritic microtubules in brain. Proc Natl Acad Sci U S A 78, 3010-3014.
186. Mccoll, G., Roberts, B.R., Gunn, A.P., Perez, K.A., Tew, D.J., Masters, C.L., Barnham, K.J., Cherny, R.A., Bush, A.I. (2009). The Caenorhabditis elegans A beta 1-42 model of Alzheimer disease predominantly expresses A beta 3-42. J Biol Chem 284, 22697-22702.
187. Mccoll, G., Roberts, B.R., Pukala, T.L., Kenche, V.B., Roberts, C.M., Link, C.D., Ryan, T.M., Masters, C.L., Barnham, K.J., Bush, A.I., Cherny, R.A. (2012). Utility of an improved model of amyloid-beta (Aβ) toxicity in Caenorhabditis elegans for drug screening for Alzheimer's disease. Mol Neurodegener 7, 57.
188. Mcdermott, J.B., Aamodt, S., Aamodt, E. (1996). ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins. Biochemistry 35, 9415-9423.
189. Mcelwee, J., Bubb, K., Thomas, J.H. (2003). Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2, 111-121.
190. Mcelwee, J.J., Schuster, E., Blanc, E., Thomas, J.H., Gems, D. (2004). Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279, 44533-44543.
191. Miyasaka, T., Ding, Z., Gengyo-Ando, K., Oue, M., Yamaguchi, H., Mitani, S., Ihara, Y. (2005). Progressive neurodegeneration in C. elegans model of tauopathy. Neurobiol Dis 20, 372-383.
192. Mizuta, K., Saito, A., Watanabe, T., Nagura, M., Arakawa, M., Shimizu, F., Hoshino, T. (1999). Ultrastructural localization of megalin in the rat cochlear duct. Hear Res 129, 83-91.
193. Morales, C.R., Igdoura, S.A., Wosu, U.A., Boman, J., Argraves, W.S. (1996). Low density lipoprotein receptor-related protein-2 expression in efferent duct and epididymal epithelia: evidence in rats for its in vivo role in endocytosis of apolipoprotein J/clusterin. Biol Reprod 55, 676-683.
194. Morley, J.F., Morimoto, R.I. (2004). Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15, 657-664.
195. Morris, J.Z., Tissenbaum, H.A., Ruvkun, G. (1996). A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382, 536-539.
196. Murakami, T., Yang, S.P., Xie, L., Kawano, T., Fu, D., Mukai, A., Bohm, C., Chen, F., Robertson, J., Suzuki, H., Tartaglia, G.G., Vendruscolo, M., Kaminski Schierle, G.S., Chan, F.T., Moloney, A., Crowther, D., Kaminski, C.F., Zhen, M., St George-Hyslop, P. (2012). ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism. Hum Mol Genet 21, 1-9.
197. Murphy, C.T., Mccarroll, S.A., Bargmann, C.I., Fraser, A., Kamath, R.S., Ahringer, J., Li, H., Kenyon, C. (2003). Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277-283.
198. Murrell, J., Farlow, M., Ghetti, B., Benson, M.D. (1991). A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254, 97-99.
199. Muñoz-Lobato, F., Rodríguez-Palero, M.J., Naranjo-Galindo, F.J., Shephard, F., Gaffney, C.J., Szewczyk, N.J., Hamamichi, S., Caldwell, K.A., Caldwell, G.A., Link, C.D., Miranda-Vizuete, A. (2014). Protective Role of DNJ-27/ERdj5 in Caenorhabditis elegans Models of Human Neurodegenerative Diseases. Antioxid Redox Signal 20, 217-235.
200. Nance, M.A. (1997). Genetic testing of children at risk for Huntington's disease. US Huntington Disease Genetic Testing Group. Neurology 49, 1048-1053.
201. Nass, R., Hahn, M.K., Jessen, T., Mcdonald, P.W., Carvelli, L., Blakely, R.D. (2005). A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-mutants impacting transporter biosynthesis and trafficking. J Neurochem 94, 774-785.
202. Nass, R., Hall, D.H., Miller, D.M., Blakely, R.D. (2002). Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc Natl Acad Sci U S A 99, 3264-3269.
203. Neumann, M., Sampathu, D.M., Kwong, L.K., Truax, A.C., Micsenyi, M.C., Chou, T.T., Bruce, J., Schuck, T., Grossman, M., Clark, C.M., Mccluskey, L.F., Miller, B.L., Masliah, E., Mackenzie, I.R., Feldman, H., Feiden, W., Kretzschmar, H.A., Trojanowski, J.Q., Lee, V.M. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133.
204. Newman, A.P., White, J.G., Sternberg, P.W. (1995). The Caenorhabditis elegans lin-12 gene mediates induction of ventral uterine specialization by the anchor cell. Development 121, 263-271.
205. Nielsen, R., Birn, H., Moestrup, S.K., Nielsen, M., Verroust, P., Christensen, E.I. (1998). Characterization of a kidney proximal tubule cell line, LLC-PK1, expressing endocytotic active megalin. J Am Soc Nephrol 9, 1767-1776.
206. Niwa, R., Hada, K. (2010). Identification of a spatio-temporal enhancer element for the Alzheimer's amyloid precursor protein-like-1 gene in the nematode Caenorhabditis elegans. Biosci Biotechnol Biochem 74, 2497-2500.
207. Niwa, R., Zhou, F., Li, C., Slack, F.J. (2008). The expression of the Alzheimer's amyloid precursor protein-like gene is regulated by developmental timing microRNAs and their targets in Caenorhabditis elegans. Dev Biol 315, 418-425.
208. Ogg, S., Paradis, S., Gottlieb, S., Patterson, G.I., Lee, L., Tissenbaum, H.A., Ruvkun, G. (1997). The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994-999.
209. Orenstein, S.J., Kuo, S.H., Tasset, I., Arias, E., Koga, H., Fernandez-Carasa, I., Cortes, E., Honig, L.S., Dauer, W., Consiglio, A., Raya, A., Sulzer, D., Cuervo, A.M. (2013). Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16, 394-406.
210. Orr, H.T., Zoghbi, H.Y. (2007). Trinucleotide repeat disorders. Annu Rev Neurosci 30, 575-621.
211. Pan, C.L., Peng, C.Y., Chen, C.H., Mcintire, S. (2011). Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons. Proc Natl Acad Sci U S A 108, 9274-9279.
212. Paradis, S., Ailion, M., Toker, A., Thomas, J.H., Ruvkun, G. (1999). A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13, 1438-1452.
213. Paradis, S., Ruvkun, G. (1998). Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12, 2488-2498.
214. Parker, J.A., Arango, M., Abderrahmane, S., Lambert, E., Tourette, C., Catoire, H., Néri, C. (2005). Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37, 349-350.
215. Parker, J.A., Connolly, J.B., Wellington, C., Hayden, M., Dausset, J., Neri, C. (2001). Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death. Proc Natl Acad Sci U S A 98, 13318-13323.
216. Pasinelli, P., Brown, R.H. (2006). Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7, 710-723.
217. Pasquier, F. (2005). Telling the difference between frontotemporal dementia and Alzheimer's disease. Curr Opin Psychiatry 18, 628-632.
218. Perez, N., Sugar, J., Charya, S., Johnson, G., Merril, C., Bierer, L., Perl, D., Haroutunian, V., Wallace, W. (1991). Increased synthesis and accumulation of heat shock 70 proteins in Alzheimer's disease. Brain Res Mol Brain Res 11, 249-254.
219. Pierce-Shimomura, J.T., Faumont, S., Gaston, M.R., Pearson, B.J., Lockery, S.R. (2001). The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature 410, 694-698.
220. Pietrzik, C.U., Yoon, I.S., Jaeger, S., Busse, T., Weggen, S., Koo, E.H. (2004). FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein. J Neurosci 24, 4259-4265.
221. Polymeropoulos, M.H., Lavedan, C., Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E.S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R.C., Di Iorio, G., Golbe, L.I., Nussbaum, R.L. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047.
222. Poorkaj, P., Bird, T.D., Wijsman, E., Nemens, E., Garruto, R.M., Anderson, L., Andreadis, A., Wiederholt, W.C., Raskind, M., Schellenberg, G.D. (1998). Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 43, 815-825.
223. Poorkaj, P., Nutt, J.G., James, D., Gancher, S., Bird, T.D., Steinbart, E., Schellenberg, G.D., Payami, H. (2004). parkin mutation analysis in clinic patients with early-onset Parkinson [corrected] disease. Am J Med Genet A 129A, 44-50.
224. Rabinovici, G.D., Miller, B.L. (2010). Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs 24, 375-398.
225. Recchia, A., Debetto, P., Negro, A., Guidolin, D., Skaper, S.D., Giusti, P. (2004). Alpha1459 synuclein and Parkinson's disease. FASEB J 18, 617-626.
226. Reinhart, B.J., Slack, F.J., Basson, M., Pasquinelli, A.E., Bettinger, J.C., Rougvie, A.E., Horvitz, H.R., Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906.
227. Renkawek, K., Voorter, C.E., Bosman, G.J., Van Workum, F.P., De Jong, W.W. (1994). Expression of alpha B-crystallin in Alzheimer's disease. Acta Neuropathol 87, 155-160.
228. Renton, A.E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J.R., Schymick, J.C., Laaksovirta, H., Van Swieten, J.C., Myllykangas, L., Kalimo, H., Paetau, A., Abramzon, Y., Remes, A.M., Kaganovich, A., Scholz, S.W., Duckworth, J., Ding, J., Harmer, D.W., Hernandez, D.G., Johnson, J.O., Mok, K., Ryten, M., Trabzuni, D., Guerreiro, R.J., Orrell, R.W., Neal, J., Murray, A., Pearson, J., Jansen, I.E., Sondervan, D., Seelaar, H., Blake, D., Young, K., Halliwell, N., Callister, J.B., Toulson, G., Richardson, A., Gerhard, A., Snowden, J., Mann, D., Neary, D., Nalls, M.A., Peuralinna, T., Jansson, L., Isoviita, V.M., Kaivorinne, A.L., Hölttä-Vuori, M., Ikonen, E., Sulkava, R., Benatar, M., Wuu, J., Chiò, A., Restagno, G., Borghero, G., Sabatelli, M., Heckerman, D., Rogaeva, E., Zinman, L., Rothstein, J.D., Sendtner, M., Drepper, C., Eichler, E.E., Alkan, C., Abdullaev, Z., Pack, S.D., Dutra, A., Pak, E., Hardy, J., Singleton, A., Williams, N.M., Heutink, P., Pickering-Brown, S., Morris, H.R., Tienari, P.J., Traynor, B.J., Consortium, I. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257-268.
229. Riddle, D.L., Swanson, M.M., Albert, P.S. (1981). Interacting genes in nematode dauer larva formation. Nature 290, 668-671.
230. Ring, S., Weyer, S.W., Kilian, S.B., Waldron, E., Pietrzik, C.U., Filippov, M.A., Herms, J., Buchholz, C., Eckman, C.B., Korte, M., Wolfer, D.P., Müller, U.C. (2007). The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice. J Neurosci 27, 7817-7826.
231. Rogaev, E.I., Sherrington, R., Rogaeva, E.A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T. (1995). Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778.
232. Ruan, Q., Harrington, A.J., Caldwell, K.A., Caldwell, G.A., Standaert, D.G. (2010). VPS41, a protein involved in lysosomal trafficking, is protective in Caenorhabditis elegans and mammalian cellular models of Parkinson's disease. Neurobiol Dis 37, 330-338.
233. Russo, T., Faraonio, R., Minopoli, G., De Candia, P., De Renzis, S., Zambrano, N. (1998). Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's beta-amyloid precursor protein. FEBS Lett 434, 1-7.
234. Sandbrink, R., Masters, C.L., Beyreuther, K. (1994). Similar alternative splicing of a non1497 homologous domain in beta A4-amyloid protein precursor-like proteins. J Biol Chem 269, 14227-14234.
235. Sastre, M., Steiner, H., Fuchs, K., Capell, A., Multhaup, G., Condron, M.M., Teplow, D.B., Haass, C. (2001). Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep 2, 835-841.
236. Savage-Dunn, C., Maduzia, L.L., Zimmerman, C.M., Roberts, A.F., Cohen, S., Tokarz, R., Padgett, R.W. (2003). Genetic screen for small body size mutants in C. elegans reveals many TGFbeta pathway components. Genesis 35, 239-247.
237. Seidel, H.S., Kimble, J. (2011). The oogenic germline starvation response in C. elegans. PLoS One 6, e28074.
238. Selkoe, D.J., Abraham, C.R., Podlisny, M.B., Duffy, L.K. (1986). Isolation of low1509 molecular-weight proteins from amyloid plaque fibers in Alzheimer's disease. J Neurochem 46, 1820-1834.
239. Shankar, G.M., Li, S., Mehta, T.H., Garcia-Munoz, A., Shepardson, N.E., Smith, I., Brett, F.M., Farrell, M.A., Rowan, M.J., Lemere, C.A., Regan, C.M., Walsh, D.M., Sabatini, B.L., Selkoe, D.J. (2008). Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14, 837-842.
240. Shaye, D.D., Greenwald, I. (2011). OrthoList: a compendium of C. elegans genes with human orthologs. PLoS One 6, e20085.
241. Shen, J., Bronson, R.T., Chen, D.F., Xia, W., Selkoe, D.J., Tonegawa, S. (1997). Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89, 629-639.
242. Sherrington, R., Rogaev, E.I., Liang, Y., Rogaeva, E.A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J.F., Bruni, A.C., Montesi, M.P., Sorbi, S., Rainero, I., Pinessi, L., Nee, L., Chumakov, I., Pollen, D., Brookes, A., Sanseau, P., Polinsky, R.J., Wasco, W., Da Silva, H.A., Haines, J.L., Perkicak-Vance, J.M., St George-Hyslop, P.H. (1995). Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754-760.
243. Shi, Z., Lu, Z., Zhao, Y., Wang, Y., Zhao-Wilson, X., Guan, P., Duan, X., Chang, Y.Z., Zhao, B. (2013). Neuroprotective effects of aqueous extracts of Uncaria tomentosa: Insights from 6-OHDA induced cell damage and transgenic Caenorhabditis elegans model. Neurochem Int 62, 940-947.
244. Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., Suzuki, T. (2000). Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25, 302-305.
245. Shinohara, H., Inaguma, Y., Goto, S., Inagaki, T., Kato, K. (1993). Alpha B crystallin and HSP28 are enhanced in the cerebral cortex of patients with Alzheimer's disease. J Neurol Sci 119, 203-208.
246. Siesling, S., Vegter-Van Der Vlis, M., Roos, R.A. (1997). Juvenile Huntington disease in the Netherlands. Pediatr Neurol 17, 37-43.
247. Simón, A.M., Schiapparelli, L., Salazar-Colocho, P., Cuadrado-Tejedor, M., Escribano, L., López De Maturana, R., Del Río, J., Pérez-Mediavilla, A., Frechilla, D. (2009). Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol Dis 33, 369-378.
248. Slunt, H.H., Thinakaran, G., Von Koch, C., Lo, A.C., Tanzi, R.E., Sisodia, S.S. (1994). Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem 269, 2637-2644.
249. So, S., Miyahara, K., Ohshima, Y. (2011). Control of body size in C. elegans dependent on food and insulin/IGF-1 signal. Genes Cells 16, 639-651.
250. Spillantini, M.G., Crowther, R.A., Kamphorst, W., Heutink, P., Van Swieten, J.C. (1998). Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am J Pathol 153, 1359-1363.
251. Sprecher, C.A., Grant, F.J., Grimm, G., O'hara, P.J., Norris, F., Norris, K., Foster, D.C. (1993). Molecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family. Biochemistry 32, 4481-4486.
252. Springer, W., Hoppe, T., Schmidt, E., Baumeister, R. (2005). A Caenorhabditis elegans Parkin mutant with altered solubility couples alpha-synuclein aggregation to proteotoxic stress. Hum Mol Genet 14, 3407-3423.
253. Sreedharan, J., Blair, I.P., Tripathi, V.B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J.C., Williams, K.L., Buratti, E., Baralle, F., De Belleroche, J., Mitchell, J.D., Leigh, P.N., Al-Chalabi, A., Miller, C.C., Nicholson, G., Shaw, C.E. (2008). TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672.
254. Steen, E., Terry, B.M., Rivera, E.J., Cannon, J.L., Neely, T.R., Tavares, R., Xu, X.J., Wands, J.R., De La Monte, S.M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis 7, 63-80.
255. Strong, T.V., Tagle, D.A., Valdes, J.M., Elmer, L.W., Boehm, K., Swaroop, M., Kaatz, K.W., Collins, F.S., Albin, R.L. (1993). Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues. Nat Genet 5, 259-265.
256. Sulston, J.E., Horvitz, H.R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56, 110-156.
257. Sumakovic, M., Hegermann, J., Luo, L., Husson, S.J., Schwarze, K., Olendrowitz, C., Schoofs, L., Richmond, J., Eimer, S. (2009). UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans. J Cell Biol 186, 897-914.
258. Tank, E.M., Rodgers, K.E., Kenyon, C. (2011). Spontaneous age-related neurite branching in Caenorhabditis elegans. J Neurosci 31, 9279-9288.
259. Terry, R.D., Gonatas, N.K., Weiss, M. (1964). ULTRASTRUCTURAL STUDIES IN ALZHEIMER'S PRESENILE DEMENTIA. Am J Pathol 44, 269-297.
260. The Huntington's Disease Collaborative Research Group. (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72(6), 971-983
261. Therrien, M., Rouleau, G.A., Dion, P.A., Parker, J.A. (2013). Deletion of C9ORF72 Results in Motor Neuron Degeneration and Stress Sensitivity in C. elegans. PLoS One 8, e83450.
262. Thinakaran, G., Borchelt, D.R., Lee, M.K., Slunt, H.H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordstedt, C., Seeger, M., Hardy, J., Levey, A.I., Gandy, S.E., Jenkins, N.A., Copeland, N.G., Price, D.L., Sisodia, S.S. (1996). Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190.
263. Thinakaran, G., Kitt, C.A., Roskams, A.J., Slunt, H.H., Masliah, E., Von Koch, C., Ginsberg, S.D., Ronnett, G.V., Reed, R.R., Price, D.L. (1995). Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci 15, 6314-6326.
264. Tissenbaum, H.A., Guarente, L. (2001). Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227-230.
265. Tomioka, M., Adachi, T., Suzuki, H., Kunitomo, H., Schafer, W.R., Iino, Y. (2006). The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans. Neuron 51, 613-625.
266. Toth, M.L., Melentijevic, I., Shah, L., Bhatia, A., Lu, K., Talwar, A., Naji, H., Ibanez-Ventoso, C., Ghose, P., Jevince, A., Xue, J., Herndon, L.A., Bhanot, G., Rongo, C., Hall, D.H., Driscoll, M. (2012). Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system. J Neurosci 32, 8778-8790.
267. Tretiakoff, K. (1919). Contribution a l'Etude de L'Anatomie pathologique du Locus Niger de Soemmering avec quelques déductions relatives à la pathogénie des troubles du tonus musculaire et De La Maladie de Parkinson. Paris.
268. Treusch, S., Hamamichi, S., Goodman, J.L., Matlack, K.E., Chung, C.Y., Baru, V., Shulman, J.M., Parrado, A., Bevis, B.J., Valastyan, J.S., Han, H., Lindhagen-Persson, M., Reiman, E.M., Evans, D.A., Bennett, D.A., Olofsson, A., Dejager, P.L., Tanzi, R.E., Caldwell, K.A., Caldwell, G.A., Lindquist, S. (2011). Functional links between Aß toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast. Science 334, 1241-1245.
269. Tsuda, H., Han, S.M., Yang, Y., Tong, C., Lin, Y.Q., Mohan, K., Haueter, C., Zoghbi, A., Harati, Y., Kwan, J., Miller, M.A., Bellen, H.J. (2008). The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell 133, 963-977.
270. Ulery, P.G., Beers, J., Mikhailenko, I., Tanzi, R.E., Rebeck, G.W., Hyman, B.T., Strickland, D.K. (2000). Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimer's disease. J Biol Chem 275, 7410-7415.
271. Vaccaro, A., Patten, S.A., Ciura, S., Maios, C., Therrien, M., Drapeau, P., Kabashi, E., Parker, J.A. (2012a). Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. PLoS One 7, e42117.
272. Vaccaro, A., Tauffenberger, A., Ash, P.E., Carlomagno, Y., Petrucelli, L., Parker, J.A. (2012b). TDP-1/TDP-43 regulates stress signaling and age-dependent proteotoxicity in Caenorhabditis elegans. PLoS Genet 8, e1002806.
273. Valentine, J.S., Doucette, P.A., Zittin Potter, S. (2005). Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. Annu Rev Biochem 74, 563-593.
274. Van Deerlin, V.M., Leverenz, J.B., Bekris, L.M., Bird, T.D., Yuan, W., Elman, L.B., Clay, D., Wood, E.M., Chen-Plotkin, A.S., Martinez-Lage, M., Steinbart, E., Mccluskey, L., Grossman, M., Neumann, M., Wu, I.L., Yang, W.S., Kalb, R., Galasko, D.R., Montine, T.J., Trojanowski, J.Q., Lee, V.M., Schellenberg, G.D., Yu, C.E. (2008). TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 7, 409-416.
275. Van Dijk, J.G., Van Der Velde, E.A., Roos, R.A., Bruyn, G.W. (1986). Juvenile Huntington disease. Hum Genet 73, 235-239
276. Van Ham, T.J., Thijssen, K.L., Breitling, R., Hofstra, R.M., Plasterk, R.H., Nollen, E.A. (2008). C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet 4, e1000027.
277. Vartiainen, S., Pehkonen, P., Lakso, M., Nass, R., Wong, G. (2006). Identification of gene expression changes in transgenic C. elegans overexpressing human alpha-synuclein. Neurobiol Dis 22, 477-486.
278. Vinceti, M., Maraldi, T., Bergomi, M., Malagoli, C. (2009). Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry. Rev Environ Health 24, 231-248.
279. Von Koch, C.S., Zheng, H., Chen, H., Trumbauer, M., Thinakaran, G., Van Der Ploeg, L.H., Price, D.L., Sisodia, S.S. (1997). Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging 18, 661-669.
280. Vonsattel, J.P., Myers, R.H., Stevens, T.J., Ferrante, R.J., Bird, E.D., Richardson, E.P. (1985). Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 44, 559-577.
281. Vowels, J.J., Thomas, J.H. (1992). Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans. Genetics 130, 105-123.
282. Wang, J., Farr, G.W., Hall, D.H., Li, F., Furtak, K., Dreier, L., Horwich, A.L. (2009). An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet 5, e1000350.
283. Wang, P., Yang, G., Mosier, D.R., Chang, P., Zaidi, T., Gong, Y.D., Zhao, N.M., Dominguez, B., Lee, K.F., Gan, W.B., Zheng, H. (2005). Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci 25, 1219-1225.
284. Wasco, W., Bupp, K., Magendantz, M., Gusella, J.F., Tanzi, R.E., Solomon, F. (1992). Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. Natl Acad Sci U S A 89, 10758-10762.
285. Wasco, W., Gurubhagavatula, S., Paradis, M.D., Romano, D.M., Sisodia, S.S., Hyman, B.T., Neve, R.L., Tanzi, R.E. (1993). Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Nat Genet 5, 95-100.
286. Weidemann, A., Eggert, S., Reinhard, F.B., Vogel, M., Paliga, K., Baier, G., Masters, C.L., Beyreuther, K., Evin, G. (2002). A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing. Biochemistry 41, 2825-2835.
287. Wen, J.Y., Kumar, N., Morrison, G., Rambaldini, G., Runciman, S., Rousseau, J., Van Der Kooy, D. (1997). Mutations that prevent associative learning in C. elegans. Behav Neurosci 111, 354-368.
288. Westlund, B., Parry, D., Clover, R., Basson, M., Johnson, C.D. (1999). Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling. Proc Natl Acad Sci U S A 96, 2497-2502.
289. Weyer, S.W., Klevanski, M., Delekate, A., Voikar, V., Aydin, D., Hick, M., Filippov, M., Drost, N., Schaller, K.L., Saar, M., Vogt, M.A., Gass, P., Samanta, A., Jäschke, A., Korte, M., Wolfer, D.P., Caldwell, J.H., Müller, U.C. (2011). APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP. EMBO J 30, 2266-2280.
290. Wheeler, J.M., Guthrie, C.R., Kraemer, B.C. (2010). The role of MSUT-2 in tau neurotoxicity: a target for neuroprotection in tauopathy? Biochem Soc Trans 38, 973-976.
291. Wiese, M., Antebi, A., Zheng, H. (2010). Intracellular trafficking and synaptic function of APL-1 in Caenorhabditis elegans. PLoS One 5.
292. Wiese, M., Antebi, A., Zheng, H. (2012). Regulation of neuronal APL-1 expression by cholesterol starvation. PLoS One 7, e32038
293. Willnow, T.E., Hilpert, J., Armstrong, S.A., Rohlmann, A., Hammer, R.E., Burns, D.K., Herz, J. (1996). Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci U S A 93, 8460-8464.
294. Willnow, T.E., Sheng, Z., Ishibashi, S., Herz, J. (1994). Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist. Science 264, 1471-1474.
295. Witan, H., Kern, A., Koziollek-Drechsler, I., Wade, R., Behl, C., Clement, A.M. (2008). Heterodimer formation of wild-type and amyotrophic lateral sclerosis-causing mutant Cu/Zn-superoxide dismutase induces toxicity independent of protein aggregation. Hum Mol Genet 17, 1373-1385.
296. Wood-Kaczmar, A., Gandhi, S., Wood, N.W. (2006). Understanding the molecular causes of Parkinson's disease. Trends Mol Med 12, 521-528.
297. Wroe, R., Wai-Ling Butler, A., Andersen, P.M., Powell, J.F., Al-Chalabi, A. (2008). ALSOD: the Amyotrophic Lateral Sclerosis Online Database. Amyotroph Lateral Scler 9, 249-250.
298. Yao, C., Johnson, W.M., Gao, Y., Wang, W., Zhang, J., Deak, M., Alessi, D.R., Zhu, X., Mieyal, J.J., Roder, H., Wilson-Delfosse, A.L., Chen, S.G. (2013). Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity. Hum Mol Genet 22, 328-344.
299. Yochem, J., Greenwald, I. (1993). A gene for a low density lipoprotein receptor-related protein in the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A 90, 4572-4576.
300. Yochem, J., Gu, T., Han, M. (1998). A new marker for mosaic analysis in Caenorhabditis elegans indicates a fusion between hyp6 and hyp7, two major components of the hypodermis. Genetics 149, 1323-1334.
301. Yochem, J., Tuck, S., Greenwald, I., Han, M. (1999). A gp330/megalin-related protein is required in the major epidermis of Caenorhabditis elegans for completion of molting. Development 126, 597-606.
302. Yokoseki, A., Shiga, A., Tan, C.F., Tagawa, A., Kaneko, H., Koyama, A., Eguchi, H., Tsujino, A., Ikeuchi, T., Kakita, A., Okamoto, K., Nishizawa, M., Takahashi, H., Onodera, O. (2008). TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 63, 538-542.
303. Yoo, B.C., Kim, S.H., Cairns, N., Fountoulakis, M., Lubec, G. (2001). Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease. Biochem Biophys Res Commun 280, 249-258.
304. Yoon, I.S., Pietrzik, C.U., Kang, D.E., Koo, E.H. (2005). Sequences from the low density lipoprotein receptor-related protein (LRP) cytoplasmic domain enhance amyloid beta protein production via the beta-secretase pathway without altering amyloid precursor protein/LRP nuclear signaling. J Biol Chem 280, 20140-20147.
305. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y.Q., Rogaeva, E., Chen, F., Kawarai, T., Supala, A., Levesque, L., Yu, H., Yang, D.S., Holmes, E., Milman, P., Liang, Y., Zhang, D.M., Xu, D.H., Sato, C., Rogaev, E., Smith, M., Janus, C., Zhang, Y., Aebersold, R., Farrer, L.S., Sorbi, S., Bruni, A., Fraser, P., St George-Hyslop, P. (2000). Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407, 48-54.
306. Zambrano, N., Bimonte, M., Arbucci, S., Gianni, D., Russo, T., Bazzicalupo, P. (2002). feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and beta1732 amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping. J Cell Sci 115, 1411-1422.
307. Zambrano, N., Buxbaum, J.D., Minopoli, G., Fiore, F., De Candia, P., De Renzis, S., Faraonio, R., Sabo, S., Cheetham, J., Sudol, M., Russo, T. (1997). Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild1737 type and mutant Alzheimer's beta-amyloid precursor proteins. J Biol Chem 272, 6399-6405.
308. Zarranz, J.J., Alegre, J., Gómez-Esteban, J.C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atarés, B., Llorens, V., Gomez Tortosa, E., Del Ser, T., Muñoz, D.G., De Yebenes, J.G. (2004). The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55, 164-173.
309. Zhang, Y.W., Luo, W.J., Wang, H., Lin, P., Vetrivel, K.S., Liao, F., Li, F., Wong, P.C., Farquhar, M.G., Thinakaran, G., Xu, H. (2005). Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. J Biol Chem 280, 17020-17026.
310. Zheng, G., Marino', M., Zhao, J., Mccluskey, R.T. (1998). Megalin (gp330): a putative endocytic receptor for thyroglobulin (Tg). Endocrinology 139, 1462-1465.
311. Zlokovic, B.V., Martel, C.L., Matsubara, E., Mccomb, J.G., Zheng, G., Mccluskey, R.T.,Frangione, B., Ghiso, J. (1996). Glycoprotein 330/megalin: probable role in receptor mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Proc Natl Acad Sci U S A 93, 4229-4234.