Neuronal death in amyotrophic lateral sclerosis (ALS): What can we learn from genetics?

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 3, 2010, Pages 259-267

  Sreedharan, J ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Amyotrophic lateral sclerosis; Fus; Genetics; Tdp 43

Indexed keywords

ALS2 PROTEIN; ALS4 PROTEIN; ALS8 PROTEIN; ALSIN; ANGIOGENIN; ARYLDIALKYLPHOSPHATASE; ARYLDIALKYLPHOSPHATASE 1; ARYLDIALKYLPHOSPHATASE 2; COPPER ZINC SUPEROXIDE DISMUTASE; DYNACTIN; FUSED IN SARCOMA TRANSLOCATED IN LIPOSARCOMA PROTEIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; MEMBRANE PROTEIN; PARAOXONASE 3; RNA BINDING PROTEIN; SENATAXIN; SYNAPTOBREVIN ASSOCIATED MEMBRANE PROTEIN B; TAR DNA BINDING PROTEIN; UNCLASSIFIED DRUG; VASCULOTROPIN;

AMYOTROPHIC LATERAL SCLEROSIS; ANGIOGENESIS; ARTICLE; BRAIN MITOCHONDRION; CELL VACUOLE; CHROMOSOME 9; DISEASE ASSOCIATION; FAMILIAL DISEASE; FRONTOTEMPORAL DEMENTIA; GENE EXPRESSION; GENE IDENTIFICATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC LINKAGE; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOME ANALYSIS; HUMAN; INTRACELLULAR TRANSPORT; MISSENSE MUTATION; NERVE CELL NECROSIS; NERVE FIBER TRANSPORT; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PHENOTYPE; PROTEIN FUNCTION; PROTEIN STRUCTURE; RNA PROCESSING; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 77954327667     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710791292558     Document Type: Article

References (145)

1. Rosen, D.R.; Siddique, T.; Patterson, D.; Figlewicz, D.A.; Sapp, P.; Hentati, A.; Donaldson, D.; Goto, J.; O'Regan, J.P.; Deng, H.X. Mutations in Cu/Zn superoxide dismutase gene are associated with Familial Amyotrophic Lateral Sclerosis. Nature, 1993, 362(6415), 59-62.
2. 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. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science, 2008, 319(5870), 1668-1672.
3. Kabashi, E.; Valdmanis, P.N.; Dion, P.; Spiegelman, D.; McConkey, B.J.; Vande, V.C.; Bouchard, J.P.; Lacomblez, L.; Pochigaeva, K.; Salachas, F.; Pradat, P.F.; Camu, W.; Meininger, V.; Dupre, N.; Rouleau, G.A. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet., 2008, 40(5), 572-574.
4. 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. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann. Neurol., 2008, 63(4), 538-542.
5. Vance, C.; Rogelj, B.; Hortobagyi, T.; De Vos, K.J.; Nishimura, A.L.; Sreedharan, J.; Hu, X.; Smith, B.; Ruddy, D.; Wright, P.; Ganesalingam, J.; Williams, K.L.; Tripathi, V.; Al-Sarraj, S.; Al-Chalabi, A.; Leigh, P.N.; Blair, I.P.; Nicholson, G.; de Belleroche, J.; Gallo, J.M.; Miller, C.C.; Shaw, C.E. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science, 2009, 323(5918), 1208-1211.
6. Kwiatkowski, T.J.; Bosco, D.A.; LeClerc, A.L.; Tamrazian, E.; Vanderburg, C.R.; Russ, C.; Davis, A.; Gilchrist, J.; Kasarkis, E.J.; Munsat, T.; Valdmanis, P.; Rouleau, G.A.; Hosler, B.A.; Cortelli, P.; de Jong, P.J.; Yoshinaga, Y.; Haines, J.L.; Pericak-Vance, M.A.; Yan, J.; Ticozzi, N.; Siddique, T.; McKenna-Yasek, D.; Sapp, P.C.; Horvitz, H.R.; Landers, J.E.; Brown, Jr., R.H. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science, 2009, 323(5918), 1205-1208.
7. Greenway, M.J.; Andersen, P.M.; Russ, C.; Ennis, S.; Cashman, S.; Donaghy, C.; Patterson, V.; Swingler, R.; Kieran, D.; Prehn, J.; Morrison, K.E.; Green, A.; Acharya, K.R.; Brown, R.H. Jr.; Hardiman, O. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat. Genet., 2006, 38(4), 411-413.
8. Graham, A.J.; Macdonald, A.M.; Hawkes, C.H. British motor neuron disease twin study. J. Neurol. Neurosurg. Psychiatry, 1997, 62(6), 562-569.
9. Fang, F.; Kamel, F.; Lichtenstein, P.; Bellocco, R.; Sparén, P.; Sandler, D.P.; Ye, W. Familial aggregation of amyotrophic lateral sclerosis. Ann. Neurol., 2009, 66(1), 94-99.
10. Andersen, P.M.; Sims, K.B.; Xin, W.W.; Kiely, R.; O'Neill, G.; Ravits, J.; Pioro, E.; Harati, Y.; Brower, R.D.; Levine, J.S.; Heinicke, H.U.; Seltzer, W.; Boss, M.; Brown, R.H. Jr. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 2003, 4(2), 62-73.
11. Shaw, C.E.; Enayat, Z.E.; Chioza, B.A.; Al-Chalabi, A.; Radunovic, A.; Powell, J.F.; Leigh, P.N. Mutations in all five exons of SOD-1 may cause ALS. Ann. Neurol., 1998, 43(3), 390-394.
12. Al-Chalabi, A.; Andersen, P.M.; Chioza, B.; Shaw, C.; Sham, P.C.; Robberecht, W.; Matthijs, G.; Camu, W.; Marklund, S.L.; Forsgren, L.; Rouleau, G.; Laing, N.G.; Hurse, P.V.; Siddique, T.; Leigh, P.N.; Powell, J.F. Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: evidence for a linked protective factor. Hum. Mol. Genet., 1998, 7(13), 2045-2050.
13. Andersen, P.M.; Forsgren, L.; Binzer, M.; Nilsson, P.; Ala-Hurula, V.; Keränen, M.L.; Bergmark, L.; Saarinen, A.; Haltia, T.; Tarvainen, I.; Kinnunen, E.; Udd, B.; Marklund, S.L. Autosomal recessive adult- onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation: a clinical and genealogical study of 36 patients. Brain, 1996, 119(4), 1153-1172. [Erratum in: Brain, 1998, 121(1), 187].
14. Broom, W.J.; Johnson, D.V.; Garber, M.; Andersen, P.M.; Lennon, N.; Landers, J.; Nusbaum, C.; Russ, C.; Brown, R.H. Jr. DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS. Neurosci. Lett., 2009, 463(1), 64-69.
15. Zinman, L.; Liu, H.N.; Sato, C.; Wakutani, Y.; Marvelle, A.F.; Moreno, D.; Morrison, K.E.; Mohlke, K.L.; Bilbao, J.; Robertson, J.; Rogaeva, E. A mechanism for low penetrance in an ALS family with a novel SOD1 deletion. Neurology, 2009, 72(13), 1153-1159.
16. Gurney, M.E.; Pu, H.; Chiu, A.Y.; Dal Canto, M.C.; Polchow, C.Y.; Alexander, D.D.; Caliendo, J.; Hentati, A.; Kwon, Y.W.; Deng, H.X. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science, 1994, 264(5166), 1772-1775.
17. Wong, P.C.; Pardo, C.A.; Borchelt, D.R.; Lee, M.K.; Copeland, N.G.; Jenkins, N.A.; Sisodia, S.S.; Cleveland, D.W.; Price, D.L. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron, 1995, 14(6), 1105-1116.
18. Reaume, A.G.; Elliott, J.L.; Hoffman, E.K.; Kowall, N.W.; Ferrante, R.J.; Siwek, D.F.; Wilcox, H.M.; Flood, D.G.; Beal, M.F.; Brown, R.H. Jr.; Scott, R.W.; Snider, W.D. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat. Genet., 1996, 13(1), 43-47.
19. Pasinelli, P.; Brown, R.H. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci., 2006, 7(9), 710-723.
20. Oosthuyse, B.; Moons, L.; Storkebaum, E.; Beck, H.; Nuyens, D.; Brusselmans, K.; Van, D.J.; Hellings, P.; Gorselink, M.; Heymans, S.; Theilmeier, G.; Dewerchin, M.; Laudenbach, V.; Vermylen, P.; Raat, H.; Acker, T.; Vleminckx, V.; Van Den, B.L.; Cashman, N.; Fujisawa, H.; Drost, M.R.; Sciot, R.; Bruyninckx, F.; Hicklin, D.J.; Ince, C.; Gressens, P.; Lupu, F.; Plate, K.H.; Robberecht, W.; Herbert, J.M.; Collen, D.; Carmeliet, P. Deletion of the hypoxia- response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat. Genet., 2001, 28(2), 131-138.
21. Chen, W.; Saeed, M.; Mao, H.; Siddique, N.; Dellefave, L.; Hung, W.Y.; Deng, H.X.; Sufit, R.L.; Heller, S.L.; Haines, J.L.; Pericak-Vance, M.; Siddique, T. Lack of association of VEGF promoter polymorphisms with sporadic ALS. Neurology, 2006, 67(3), 508-510.
22. Gros-Louis, F.; Laurent, S.; Lopes, A.A.; Khoris, J.; Meininger, V.; Camu, W.; Rouleau, G.A. Absence of mutations in the hypoxia response element of VEGF in ALS. Muscle Nerve, 2003, 28(6), 774-775.
23. Lambrechts, D.; Storkebaum, E.; Morimoto, M.; Del-Favero, J.; Desmet, F.; Marklund, S.L.; Wyns, S.; Thijs, V.; Andersson, J.; van Marion, I.; Al-Chalabi, A.; Bornes, S.; Musson, R.; Hansen, V.; Beckman, L.; Adolfsson, R.; Pall, H.S.; Prats, H.; Vermeire, S.; Rutgeerts, P.; Katayama, S.; Awata, T.; Leigh, N.; Lang-Lazdunski, L.; Dewerchin, M.; Shaw, C.; Moons, L.; Vlietinck, R.; Morrison, K.E.; Robberecht, W.; Van, B.C.; Collen, D.; Andersen, P.M.; Carmeliet, P. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat. Genet., 2003, 34(4), 383-394.
24. Van Vught, P.W.; Sutedja, N.A.; Veldink, J.H.; Koeleman, B.P.; Groeneveld, G.J.; Wijmenga, C.; Uitdehaag, B.M.; de Jong, J.M.; Baas, F.; Wokke, J.H.; Van den Berg, L.H. Lack of association between VEGF polymorphisms and ALS in a Dutch population. Neurology, 2005, 65(10), 1643-1645.
25. Fernández-Santiago, R.; Sharma, M.; Mueller, J.C.; Gohlke, H.; Illig, T.; Anneser, J.; Münch, C.; Ludolph, A.; Kamm, C.; Gasser, T. Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS. Neurology, 2006, 66(12), 1929-1931.
26. Lambrechts, D.; Poesen, K.; Fernández-Santiago, R.; Al-Chalabi, A.; Del Bo, R.; Van Vught, P.W.; Khan, S.; Marklund, S.; Brockington, A.; Van Marion, I.; Anneser, J.; Shaw, C.; Ludolph, A.; Leigh, N.; Comi, G.; Gasser, T.; Shaw, P.J.; Morrison, K.; Andersen, P.; Van den Berg, L.H.; Thijs, V.; Siddique, T.; Robberecht, W.; Carmeliet, P. Meta-analysis of VEGF variations in ALS: increased susceptibility in male carriers of the -2578AA genotype. J. Med. Genet., 2009, 46(12), 840-846.
27. Greenway, M.J.; Alexander, M.D.; Ennis, S.; Traynor, B.J.; Corr, B.; Frost, E.; Green, A.; Hardiman, O. A novel candidate region for ALS on chromosome 14q11.2. Neurology, 2004, 63(10), 1936-1938.
28. Wu, D.; Yu, W.; Kishikawa, H.; Folkerth, R.D.; Iafrate, A.J.; Shen, Y.; Xin, W.; Sims, K.; Hu, G.F. Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis. Ann. Neurol., 2007, 62(6), 609-617.
29. van Es, M.A.; Diekstra, F.P.; Veldink, J.H.; Baas, F.; Bourque, P.R.; Schelhaas, H.J.; Strengman, E.; Hennekam, E.A.; Lindhout, D.; Ophoff, R.A.; van den Berg, L.H. A case of ALS-FTD in a large FALS pedigree with a K17I ANG mutation. Neurology, 2009, 72(3), 287-288.
30. Seilhean, D.; Cazeneuve, C.; Thuriès, V.; Russaouen, O.; Millecamps, S.; Salachas, F.; Meininger, V.; Leguern, E.; Duyckaerts, C. Accumulation of TDP-43 and alpha-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation. Acta Neuropathol., 2009, 118(4), 561-573.
31. Fett, J.W.; Strydom, D.J.; Lobb, R.R.; Alderman, E.M.; Bethune, J.L.; Riordan, J.F.; Vallee, B.L. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry, 1985, 24(20), 5480-5486.
32. Xu, Z.P.; Tsuji, T.; Riordan, J.F.; Hu, G.F. Identification and characterization of an angiogenin-binding DNA sequence that stimulates luciferase reporter gene expression. Biochemistry, 2003, 42(1), 121-128.
33. Kishimoto, K.; Liu, S.; Tsuji, T.; Olson, K.A.; Hu, G.F. Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis. Oncogene, 2005, 24(3), 445-456.
34. Yamasaki, S.; Ivanov, P.; Hu, G.F.; Anderson, P. Angiogenin cleaves tRNA and promotes stress-induced translational repression. J. Cell. Biol., 2009, 185(1), 35-42.
35. 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. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 2006, 314, 130-133.
36. Arai, T.; Hasegawa, M.; Akiyama, H.; Ikeda, K.; Nonaka, T.; Mori, H.; Mann, D.; Tsuchiya, K.; Yoshida, M.; Hashizume, Y.; Oda, T. TDP-43 is a component of ubiquitin-positive taunegative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun., 2006, 351, 602-611.
37. Corrado, L.; Ratti, A.; Gellera, C.; Buratti, E.; Castellotti, B.; Carlomagno, Y.; Ticozzi, N.; Mazzini, L.; Testa, L.; Taroni, F.; Baralle, F.E.; Silani, V.; D'Alfonso, S. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum. Mutat., 2009, 30(4), 688-694.
38. Del Bo, R.; Grezzi, S.; Corti, S.; Pandolfo, M.; Ranieri, M.; Santoro, D.; Ghigne, I.; Pelle, A.; Orsetti, V.; Mancuso, M.; Sorarù, G.; Briani, C.; Angelici, C.; Siciliano, G.; Bresolin, N.; Comi, G.P. TARDBP (TDP-43) sequence analysis in patients with familial and sporadic ALS: identification of two novel mutations. Eur. J. Neurol., 2009, 16(6), 727-732.
39. rd; Bigio, E.H.; Caselli, R.; Baker, M.; Al-Lozi, M.T.; Morris, J.C.; Pestronk, A.; Rademakers, R.; Goate, A.M.; Cairns, N.J. TDP-43 A315T mutation in familial motor neuron disease. Ann. Neurol., 2008, 63(4), 535-538.
40. Kühnlein, P.; Sperfeld, A.D.; Vanmassenhove, B.; Van Deerlin, V.; Lee, V.M.Y.; Trojanowski, J.Q.; Kretzschmar, H.A.; Ludolph, A.C.; Neumann, M. Two German kindreds with familial amytrophic lateral sclerosis due to TARDBP mutations. Arch. Neurol., 2008, 65, 1185-1189.
41. Lemmens, R.; Race, V.; Hersmus, N.; Matthijs, G.; Van Den Bosch, L.; Van Damme, P.; Dubois, B.; Boonen, S.; Goris, A.; Robberecht, W. TDP-43 M311V mutation in familial amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry, 2009, 80(3), 354-355.
42. Rutherford, N.J.; Zhang, Y.J.; Baker, M.; Gass, J.M.; Finch, N.A.; Xu, Y.F.; Stewart, H., Kelley, B.J.; Kuntz, K.; Crook, R.J.; Sreedharan, J.; Vance, C.; Sorenson, E.; Lippa, C.; Bigio, E.H.; Geschwind, D.H.; Knopman, D.S.; Mitsumoto, H.; Petersen, R.C.; Cashman, N.R.; Hutton, M.; Shaw, C.E.; Boylan, K.B.; Boeve, B.; Graff-Radford, N.R.; Wszolek, Z.K.; Caselli, R.J.; Dickson, D.W.; Mackenzie, I.R.; Petrucelli, L.; Rademakers, R. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet., 2008, 4(9), e1000193.
43. 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. TARDBP mutations in amyotrophic lateral sclerosis with TDP- J. Sreedharan 43 neuropathology: a genetic and histological analysis. Lancet Neurol., 2008, 7(5), 409-416.
44. Kamada, M.; Maruyama, H.; Tanaka, E.; Morino, H.; Wate, R.; Ito, H.; Kusaka, H.; Kawano, Y.; Miki, T.; Nodera, H.; Izumi, Y.; Kaji, R.; Kawakami, H. Screening for TARDBP mutations in Japanese familial amyotrophic lateral sclerosis. J. Neurol. Sci., 2009, 284(1-2), 69-71.
45. Benajiba, L.; Le Ber, I.; Camuzat, A.; Lacoste, M.; Thomas-Anterion, C.; Couratier, P.; Legallic, S.; Salachas, F.; Hannequin, D.; Decousus, M.; Lacomblez, L.; Guedj, E.; Golfier, V.; Camu, W.; Dubois, B.; Campion, D.; Meininger, V.; Brice, A. French clinical and genetic research network on frontotemporal lobar degeneration/fronto- temporal lobar degeneration with motoneuron disease. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann. Neurol., 2009, 65(4), 470-473.
46. Kovacs, G.G.; Murrell, J.R.; Horvath, S.; Haraszti, L.; Majtenyi, K.; Molnar, M.J., Budka, H.; Ghetti, B.; Spina, S. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov. Disord., 2009, 24(12), 1843-1847.
47. Borroni, B.; Bonvicini, C.; Alberici, A.; Buratti, E.; Agosti, C.; Archetti, S.; Papetti, A.; Stuani, C.; Di Luca, M.; Gennarelli, M.; Padovani, A. Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum. Mutat., 2009, 30(11), E974-E983.
48. Buratti, E.; Baralle, F.E. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front. Biosci., 2008, 13, 867-878.
49. Abhyankar, M.M.; Urekar, C.; Reddi, P.P. A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in somatic tissues: role for TDP-43 in insulator function. J. Biol. Chem., 2007, 282(50), 36143-36154.
50. Johnson, B.S.; McCaffery, J.M.; Lindquist, S.; Gitler, A.D. A yeast TDP-43 proteinopathy model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc. Natl. Acad. Sci. USA, 2008, 105(17), 6439-6444.
51. Elvira, G.; Wasiak, S.; Blandford, V.; Tong, X.K.; Serrano, A.; Fan, X.; del Rayo Sanchez-Carbente, M.; Servant, F.; Bell, A.W.; Boismenu, D.; Lacaille, J.C.; McPherson, P.S.; DesGroseillers, L.; Sossin, W.S. Characterization of an RNA granule from developing brain. Mol. Cell. Proteomics, 2006, 5(4), 635-651.
52. Wang, I.F.; Wu, L.S.; Chang, H.Y.; Shen, C.K. TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. J. Neurochem., 2008, 105(3), 797-806.
53. Moisse, K.; Volkening, K.; Leystra-Lantz, C.; Welch, I.; Hill, T.; Strong, M.J. Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res., 2009, 1249, 202-211.
54. Wegorzewska, I.; Bell, S.; Cairns, N.J.; Miller, T.M.; Baloh, R.H. TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc. Natl. Acad. Sci. USA, 2009, 106(44),18809-18814.
55. Abalkhail, H.; Mitchell, J.; Habgood, J.; Orrell, R.; de Belleroche, J. A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2. Am. J. Hum. Genet., 2003, 73(2), 383-389.
56. Ruddy, D.M.; Parton, M.J.; Al-Chalabi, A.; Lewis, C.M.; Vance, C.; Smith, B.N.; Leigh, P.N.; Powell, J.F.; Siddique, T.; Meyjes, E.P.; Baas, F.; de Jong, V.; Shaw, C.E. Two families with familial amyotrophic lateral sclerosis are linked to a novel locus on chromosome 16q. Am. J. Hum. Genet., 2003, 73(2), 390-396.
57. Sapp, P.C.; Hosler, B.A.; McKenna-Yasek, D.; Chin, W.; Gann, A.; Genise, H.; Gorenstein, J.; Huang, M.; Sailer, W.; Scheffler, M.; Valesky, M.; Haines, J.L.; Pericak-Vance, M.; Siddique, T.; Horvitz, H.R.; Brown, R.H. Jr. Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Am. J. Hum. Genet., 2003, 73(2), 397-403.
58. Vance, C.; Al-Chalabi, A.; Ruddy, D.; Smith, B.N.; Hu, X.; Sreedharan, J.; Siddique, T.; Schelhaas, H.J.; Kusters, B.; Troost, D.; Baas, F.; de Jong, V.; Shaw, C.E. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain, 2006, 129(Pt 4), 868-876.
59. Kwiatkowski, T.J., Jr.; Bosco, D.A.; Leclerc, A.L.; Tamrazian, E.; Vanderburg, C.R.; Russ, C.; Davis, A.; Gilchrist, J.; Kasarskis, E.J.; Munsat, T.; Valdmanis, P.; Rouleau, G.A.; Hosler, B.A.; Cortelli, P.; de Jong, P.J.; Yoshinaga, Y.; Haines, J.L.; Pericak-Vance, M.A.; Yan, J.; Ticozzi, N.; Siddique, T.; McKenna-Yasek, D.; Sapp, P.C.; Horvitz, H.R.; Landers, J.E; Brown, R.H. Jr. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science, 2009, 323(5918), 1205-1208.
60. Belzil, V.V.; Valdmanis, P.N.; Dion, P.A.; Daoud, H.; Kabashi, E.; Noreau, A.; Gauthier, J.; S2D team.; Hince, P.; Desjarlais, A.; Bouchard, J.P.; Lacomblez, L.; Salachas, F.; Pradat, P.F.; Camu, W.; Meininger, V.; Dupré, N.; Rouleau, G.A. Mutations in FUS cause FALS and SALS in French and French Canadian populations. Neurology, 2009, 73(15), 1176-1179.
61. Ticozzi, N.; Silani, V.; LeClerc, A.L.; Keagle, P.; Gellera, C.; Ratti, A.; Taroni, F.; Kwiatkowski, T.J., Jr.; McKenna-Yasek, D.M.; Sapp, P.C.; Brown, R.H., Jr.; Landers, J.E. Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis within an Italian cohort. Neurology, 2009, 73(15),1180-1185.
62. Chiò, A.; Restagno, G.; Brunetti, M.; Ossola, I.; Calvo, A.; Mora, G.; Sabatelli, M.; Monsurrò, M.R.; Battistini, S.; Mandrioli, J.; Salvi, F.; Spataro, R.; Schymick, J.; Traynor, B.J.; La Bella, V.; ITALSGEN Consortium. Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation. Neurobiol. Aging, 2009, 30(8), 1272-1275.
63. Corrado, L.; Del, Bo, R.; Castellotti, B.; Ratti, A.; Cereda, C.; Penco, S.; Sorarù, G.; Carlomagno, Y.; Ghezzi, S.; Pensato, V.; Colombrita, C.; Gagliardi, S.; Cozzi, L.; Orsetti, V.; Mancuso, M.; Siciliano, G.; Mazzini, L.; Comi, G.P.; Gellera, C.; Ceroni, M.; D'Alfonso, S.; Silani, V. Mutations of FUS Gene in Sporadic Amyotrophic Lateral Sclerosis. J. Med. Genet., 2009, 47, 190-194.
64. Van Damme, P.; Goris, A.; Race, V.; Hersmus, N.; Dubois, B.; Bosch, L.V.; Matthijs, G.; Robberecht, W. The occurrence of mutations in FUS in a Belgian cohort of patients with familial ALS. Eur. J. Neurol., 2009, [Epub ahead of print].
65. Blair, I.P.; Williams, K.L.; Warraich, S.T.; Durnall, J.C.; Thoeng, A.D.; Manavis, J.; Blumbergs, P.C.; Vucic, S.; Kiernan, M.C.; Nicholson, G.A. FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis. J. Neurol. Neurosurg. Psychiatry, 2009, doi: 10.1136/jnnp.2009.194 399.
66. Tateishi, T.; Hokonohara, T.; Yamasaki, R.; Miura, S.; Kikuchi, H.; Iwaki, A.; Tashiro, H.; Furuya, H.; Nagara, Y.; Ohyagi, Y.; Nukina, N.; Iwaki, T.; Fukumaki, Y.; Kira, J.I. Multiple system degeneration with basophilic inclusions in Japanese ALS patients with FUS mutation. Acta Neuropathol., 2010, 119(3), 355-364.
67. Drepper, C.; Herrmann, T.; Wessig, C.; Beck, M.; Sendtner, M. C- terminal FUS/TLS mutations in familial and sporadic ALS in Germany. Neurobiol. Aging, 2009, [Epub ahead of print].
68. Law, W.J.; Cann, K.L.; Hicks, G.G. TLS, EWS and TAF15: a model for transcriptional integration of gene expression. Brief Funct. Genom. Proteomic, 2006, 5(1), 8-14.
69. Uranishi, H.; Tetsuka, T.; Yamashita, M.; Asamitsu, K.; Shimizu, M.; Itoh, M.; Okamoto, T. Involvement of the pro-oncoprotein TLS (translocated in liposarcoma) in nuclear factor-kappa B p65-mediated transcription as a coactivator. J. Biol. Chem., 2001, 276(16), 13395-13401.
70. Wang, X.; Arai, S.; Song, X.; Reichart, D.; Du, K.; Pascual, G.; Tempst, P.; Rosenfeld, M.G.; Glass, C.K.; Kurokawa, R. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature, 2008, 454(7200), 126-130.
71. Hicks, G.G.; Singh, N.; Nashabi, A.; Mai, S.; Bozek, G.; Klewes, L.; Arapovic, D.; White, E.K.; Koury, M.J.; Oltz, E.M.; Van Kaer, L.; Ruley, H.E. Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nat. Genet., 2000, 24(2), 175-179.
72. Gregory, R.I.; Yan, K.P.; Amuthan, G.; Chendrimada, T.; Doratotaj, B.; Cooch, N.; Shiekhattar, R. The Microprocessor complex mediates the genesis of microRNAs. Nature, 2004, 432(7014), 235-240.
73. Zinszner, H.; Sok, J.; Immanuel, D.; Yin, Y.; Ron, D. TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling. J. Cell. Sci., 1997, 110(Pt 15), 1741-1750.
74. Yoshimura, A.; Fujii, R.; Watanabe, Y.; Okabe, S.; Fukui, K.; Takumi, T. Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines. Curr. Biol., 2006, 16(23), 2345-2351.
75. Kanai, Y.; Dohmae, N.; Hirokawa, N. Kinesin transports RNA: isolation and characterisation of an RNA-transporting granule. Neuron, 2004, 43(4), 513-525.
76. Zinszner, H.; Albalat, R.; Ron D. A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes Dev., 1994, 8(21), 2513-2526.
77. Yang, L.; Embree, L.J.; Tsai, S.; Hickstein, D.D. Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing. J. Biol. Chem., 1998, 273(43), 27761-27764.
78. Neumann, M.; Rademakers, R.; Roeber, S.; Baker, M.; Kretzschmar, H.A.; Mackenzie, I.R. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain, 2009, 132(Pt 11), 2922-2931.
79. Munoz, D.G.; Neumann, M.; Kusaka, H.; Yokota, O.; Ishihara, K.; Terada, S.; Kuroda, S.; Mackenzie, I.R. FUS pathology in basophilic inclusion body disease. Acta Neuropathol., 2009, 118, 617-627.
80. Hentati, A.; Bejaoui, K.; Pericak-Vance, M.A.; Hentati, F.; Speer, M.C.; Hung, W.Y.; Figlewicz, D.A.; Haines, J.; Rimmler, J.; Ben Hamida, C.; Ben Hamida, M.; Brown, R.H., Jr.; Siddique, T. Linkage of recessive familial amyotrophic lateral sclerosis to chromosome 2q33-q35. Nat. Genet., 1994, 7(3), 425-428.
81. Hadano, S.; Hand, C.K.; Osuga, H.; Yanagisawa, Y.; Otomo, A.; Devon, R.S.; Miyamoto, N.; Showguchi-Miyata, J.; Okada, Y.; Singaraja, R.; Figlewicz, D.A.; Kwiatkowski, T.; Hosler, B.A.; Sagie, T.; Skaug, J.; Nasir, J.; Brown, R.H. Jr.; Scherer, S.W.; Rouleau, G.A.; Hayden, M.R.; Ikeda, J.E. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet., 2001, 29(2), 166-173.
82. Yang, Y.; Hentati, A.; Deng, H.X.; Dabbagh, O.; Sasaki, T.; Hirano, M.; Hung, W.Y.; Ouahchi, K.; Yan, J.; Azim, A.C.; Cole, N.; Gascon, G.; Yagmour, A.; Ben-Hamida, M.; Pericak-Vance, M.; Hentati, F.; Siddique, T. The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat. Genet., 2001, 29(2), 160-165.
83. Devon, R.S.; Helm, J.R.; Rouleau, G.A.; Leitner, Y.; Lerman-Sagie, T.; Lev, D.; Hayden, M.R. The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. Clin. Genet., 2003, 64(3), 210-215.
84. Eymard-Pierre, E.; Lesca, G.; Dollet, S.; Santorelli, F.M.; Di Capua, M.; Bertini, E.; Boespflug-Tanguy, O. Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. Am. J. Hum. Genet., 2002, 71(3), 518-527.
85. Gros-Louis, F.; Meijer, I.A.; Hand, C.K.; Dube, M.P.; MacGregor, D.L.; Seni, M.H.; Devon, R.S.; Hayden, M.R.; Andermann, F.; Andermann, E.; Rouleau, G.A. An ALS2 gene mutation causes hereditary spastic paraplegia in Pakistani kindred. Ann. Neurol., 2003, 53(1), 144-145.
86. Yamanaka, K.; Vande, V.C.; Eymard-Pierre, E.; Bestini, E.; Boespflug-Tanguy, O.; Cleveland, D.W. Unstable mutants in the peripheral endosomal membrane component ALS2 cause early-onset motor neuron disease. Proc. Natl. Acad. Sci. USA, 2003, 100(26), 16041-16046.
87. Otomo, A.; Hadano, S.; Okada, T.; Mizumura, H.; Kunita, R.; Nishijima, H.; Showguchi-Miyata, J.; Yanagisawa, Y.; Kohiki, E.; Suga, E.; Yasuda, M.; Osuga, H.; Nishimoto, T.; Narumiya, S.; Ikeda, J.E. ALS2, a novel guanine nucleotide exchange factor for the small GTPase Rab5, is implicated in endosomal dynamics. Hum. Mol. Genet., 2003, 12(14), 1671-1687.
88. Topp, J.D.; Gray, N.W.; Gerard, R.D.; Horazdovsky, B.F. Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. J. Biol. Chem., 2004, 279(23), 24612-24623.
89. Kanekura, K.; Hashimoto, Y.; Niikura, T.; Aiso, S.; Matsuoka, M.; Nishimoto, I. Alsin, the product of ALS2 gene, suppresses SOD1 mutant neurotoxicity through RhoGEF domain by interacting with SOD1 mutants. J. Biol. Chem., 2004, 279(18), 19247-19256.
90. Tudor, E.L.; Perkinton, M.S.; Schmidt, A.; Ackerley, S.; Brownlees, J.; Jacobsen, N.J.; Byers, H.L.; Ward, M.; Hall, A.; Leigh, P.N.; Shaw, C.E.; McLoughlin, D.M.; Miller, C.C. ALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth. J. Biol. Chem., 2005, 280(41), 34735-34740.
91. Chance, P.F.; Rabin, B.A.; Ryan, S.G.; Ding, Y.; Scavina, M.; Crain, B.; Griffin, J.W.; Cornblath, D.R. Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. Am. J. Hum. Genet., 1998, 62(3), 633-640.
92. Chen, Y.Z.; Bennett, C.L; Huynh, H.M.; Blair, I.P.; Puls, I.; Irobi, J.; Dierick, I.; Abel, A.; Kennerson, M.L.; Rabin, B.A.; Nicholson, G.A.; Auer-Grumbach, M.; Wagner, K.; De Jonghe, P.; Griffin, J.W.; Fischbeck, K.H.; Timmerman, V.; Cornblath, D.R.; Chance, P.F. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am. J. Hum. Genet., 2004, 74(6), 1128-1135.
93. Moreira, M.C.; Klur, S.; Watanabe, M.; Nemeth, A.H.; Le Ber, I.; Moniz, J.C.; Tranchant, C.; Aubourg, P.; Tazir, M.; Schols, L.; Pandolfo, M.; Schulz, J.B.; Pouget, J.; Calvas, P.; Shizuka-Ikeda, M.; Shoji, M.; Tanaka, M.; Izatt, L.; Shaw, C.E.; M'Zahem, A.; Dunne, E.; Bomont, P.; Benhassine, T.; Bouslam, N.; Stevanin, G.; Brice, A.; Guimaraes, J.; Mendonca, P.; Barbot, C.; Coutinho, P.; Sequeiros, J.; Durr, A.; Warter, J.M.; Koenig, M. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat. Genet., 2004, 36(3), 225-227.
94. Grohmann, K.; Schuelke, M.; Diers, A.; Hoffmann, K.; Lucke, B.; Adams, C.; Bertini, E.; Leonhardt-Horti, H.; Muntoni, F.; Ouvrier, R.; Pfeufer, A.; Rossi, R.; Van Maldergem, L.; Wilmshurst, J.M.; Wienker, T.F.; Sendtner, M.; Rudnik-Schoneborn, S.; Zerres, K.; Hubner, C. Mutations in the gene encoding immunoglobulin mu- binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat. Genet., 2001, 29(1), 75-77.
95. Nishimura, A.L.; Mitne-Neto, M.; Silva, H.C.A.; Oliveira, J.R.M.; Vainzof, M.; Zatz, M. A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13. J. Med. Genet., 2004, 41, 315-320.
96. Nishimura, A.L.; Mitne-Neto, M.; Silva, H.C.A.; Richieri-Costa, A.; Middleton, S.; Cascio D.; Kok, F.; Oliveira, J.R.; Gillingwater, T.; Webb, J.; Skehel, P.; Zatz, M. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet., 2004, 75, 822-831.
97. Nishimura, A.L.; Al-Chalabi, A.; Zatz, M. A common founder for amyotrophic lateral sclerosis type 8(ALS8) in the Brazilian population. Hum. Genet., 2005, 118(3-4), 499-500.
98. Ricard, J.; Salinas, J.; Garcia, L.; Liebl, D.J. EphrinB3 regulates cell proliferation and survival in adult neurogenesis. Mol. Cell. Neurosci., 2006, 31(4), 713-722.
99. 2+/calmodulin-dependent protein kinase II activation during C. elegans oocyte meiotic maturation. Development, 2005, 132(23), 5225-5237.
100. Dalva, M.B.; Takasu, M.A.; Lin, M.Z.; Shamah, S.M.; Hu, L.; Gale, N.W.; Greenberg, M.E. EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell, 2000, 103(6), 945-956.
101. Kihira, T.; Utunomiya, H.; Kondo, T. Expression of FKBP12 and ryanodine receptors (RyRs) in the spinal cord of MND patients. Amyotroph. Lateral. Scler. Other Motor Neuron Disord., 2005, 6(2), 94-99.
102. Puls, I.; Jonnakuty, C.; LaMonte, B.H.; Holzbaur, E.L.; Tokito, M.; Mann, E.; Floeter, M.K.; Bidus, K.; Drayna, D.; Oh, S.J.; Brown, R.H., Jr.; Ludlow, C.L.; Fischbeck, K.H. Mutant dynactin in motor neuron disease. Nat. Genet., 2003, 33(4), 455-456.
103. Münch, C.; Sedlmeier, R.; Meyer, T.; Homberg, V.; Sperfeld, A.D.; Kurt, A.; Prudlo, J.; Peraus, G.; Hanemann, C.O.; Stumm, G.; Ludolph, A.C. Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology, 2004, 63(4), 724-726.
104. Munch, C.; Rosenbohm, A.; Sperfeld, A.D.; Uttner, I.; Reske, S.; Krause, B.J.; Sedlmeier, R.; Meyer, T.; Hanemann, C.O.; Stumm, G.; Ludolph, A.C. Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD. Ann. Neurol., 2005, 58(5), 777-780.
105. De Vos, K.J.; Grierson, A.J.; Ackerley, S.; Miller, C.C. Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci., 2008, 31, 151-173.
106. Lindberg, M.J.; Byström, R.; Boknäs, N.; Andersen, P.M.; Oliveberg, M. Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants. Proc. Natl. Acad. Sci. USA, 2005, 102(28), 9754-9759.
107. Dunckley, T.; Huentelman, M.J.; Craig, D.W.; Pearson, J.V.; Szelinger, S.; Joshipura, K.; Halperin, R.F.; Stamper, C.; Jensen, K.R.; Letizia, D.; Hesterlee, S.E.; Pestronk, A.; Levine, T.; Bertorini, T.; Graves, M.C.; Mozaffar, T.; Jackson, C.E.; Bosch, P.; McVey, A.; Dick, A.; Barohn, R.; Lomen-Hoerth, C.; Rosenfeld, J.; O'connor, D.T.; Zhang, K.; Crook, R.; Ryberg, H.; Hutton, M.; Katz, J.; Simpson, E.P.; Mitsumoto, H.; Bowser, R.; Miller, R.G.; Appel, S.H.; Stephan, D.A. Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N. Engl. J. Med., 2007, 357(8), 775-788.
108. van Es, M.A.; van Vught, P.W.; Blauw, H.M.; Franke, L.; Saris, C.G.; Andersen, P.M.; Van Den Bosch, L.; de Jong, S.W.; van 't Slot, R.; Birve, A.; Lemmens, R.; de Jong, V.; Baas, F.; Schelhaas, H.J.; Sleegers, K.; Van Broeckhoven, C.; Wokke, J.H.; Wijmenga, C.; Robberecht, W.; Veldink, J.H.; Ophoff, R.A.; Van den Berg, L.H. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol., 2007, 6(10), 869-877.
109. van Es, M.A.; van Vught, P.W.; Blauw, H.M.; Franke, L.; Saris, C.G.; Van den Bosch, L.; de Jong, S.W.; de Jong, V.; Baas, F.; van't, S.R.; Lemmens, R.; Schelhaas, H.J.; Birve, A.; Sleegers, K.; Van Broeckhoven, C.; Schymick, J.C.; Traynor, B.J.; Wokke, J.H.; Wijmenga, C.; Robberecht, W.; Andersen, P.M.; Veldink, J.H.; Ophoff, R.A.; Van den Berg, L.H. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nat. Genet., 2008, 40(1), 29-31.
110. van Es, M.A.; Veldink, J.H.; Saris, C.G.; Blauw, H.M.; van Vught, P.W.; Birve, A.; Lemmens, R.; Schelhaas, H.J.; Groen, E.J.; Huisman, M.H.; van der Kooi, A.J.; de Visser, M.; Dahlberg, C.; Estrada, K.; Rivadeneira, F.; Hofman, A.; Zwarts, M.J.; van Doormaal, P.T.; Rujescu, D.; Strengman, E.; Giegling, I.; Muglia, P.; Tomik, B.; Slowik, A.; Uitterlinden, A.G.; Hendrich, C.; Waibel, S.; Meyer, T.; Ludolph, A.C.; Glass, J.D.; Purcell, S.; Cichon, S.; Nöthen, M.M.; Wichmann, H.E.; Schreiber, S.; Vermeulen, S.H.; Kiemeney, L.A.; Wokke, J.H.; Cronin, S.; McLaughlin, R.L.; Hardiman, O.; Fumoto, K.; Pasterkamp, R.J.; Meininger, V.; Melki, J.; Leigh, P.N.; Shaw, C.E.; Landers, J.E., Al-Chalabi, A.; Brown, R.H., Jr.; Robberecht, W.; Andersen, P.M.; Ophoff, R.A.; van den Berg, L.H. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat. Genet., 2009, 41(10), 1083-1087.
111. Simpson, C.L.; Lemmens, R.; Miskiewicz, K.; Broom, W.J.; Hansen, V.K.; Van Vught, P.W.; Landers, J.E.; Sapp, P.; Van Den Bosch, L.; Knight, J.; Neale, B.M.; Turner, M.R.; Veldink, J.H.; Ophoff, R.A.; Tripathi, V.B.; Beleza, A.; Shah, M.N.; Proitsi, P.; Van Hoecke, A.; Carmeliet, P.; Horvitz, H.R.; Leigh, P.N.; Shaw, C.E.; Van den Berg, L.H.; Sham, P.C.; Powell, J.F.; Verstreken, P.; Brown, R.H., Jr.; Robberecht, W.; Al-Chalabi, A. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Hum. Mol. Genet., 2008, 18(3), 472-481.
112. Winkler, G.S.; Kristjuhan, A.; Erdjument-Bromage, H.; Tempst, P.; Svejstrup, J.Q. Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proc. Natl. Acad. Sci. USA, 2002, 99(6), 3517-3522.
113. Landers, J.E.; Melki, J.; Meininger, V.; Glass, J.D.; van den Berg, L.H.; van Es, M.A.; Sapp, P.C.; van Vught, P.W.; McKenna-Yasek, D.M.; Blauw, H.M.; Cho, T.J.; Polak, M.; Shi, L.; Wills, A.M.; Broom, W.J.; Ticozzi, N.; Silani, V.; Ozoguz, A.; Rodriguez-Leyva, I.; Veldink, J.H.; Ivinson, A.J.; Saris, C.G.; Hosler, B.A.; Barnes- Nessa, A.; Couture, N.; Wokke, J.H.; Kwiatkowski, T.J., Jr.; Ophoff, R.A.; Cronin, S.; Hardiman, O.; Diekstra, F.P.; Leigh, P.N.; Shaw, C.E.; Simpson, C.L.; Hansen, V.K.; Powell, J.F.; Corcia, P.; Salachas, F.; Heath, S.; Galan, P.; Georges, F.; Horvitz, H.R.; Lathrop, M.; Purcell, S.; Al-Chalabi, A.; Brown, R.H., Jr. Reduced expression of the Kinesin-Associated Protein 3(KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA, 2009, 106(22), 9004-9009.
114. Al-Chalabi, A.; Andersen, P.M.; Nilsson, P.; Chioza, B.; Andersson, J.L.; Russ, C.; Shaw, C.E.; Powell, J.F.; Leigh, P.N. Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum. Mol. Genet., 1999, 8, 157-164.
115. Figlewicz, D.A.; Krizus, A.; Martinoli, M.G.; Meininger, V.; Dib, M.; Rouleau, G.A.; Julien, J.P. Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum. Mol. Genet., 1994, 3(10), 1757-1761.
116. Tomkins, J.; Usher, P.; Slade, J.Y.; Ince, P.G.; Curtis, A.; Bushby, K.; Shaw, P.J. Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport, 1998, 9(17), 3967-3970.
117. Gros-Louis, F.; Lariviere, R.; Gowing, G.; Laurent, S.; Camu, W.; Bouchard, J.P.; Meininger, V.; Rouleau, G.A.; Julien, J.P. A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J. Biol. Chem., 2004, 279(44), 45951-45956.
118. Leung, C.L.; He, C.Z.; Kaufmann, P.; Chin, S.S.; Naini, A.; Liem, R.K.; Mitsumoto, H.; Hays, A.P. A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis. Brain Pathol., 2004, 14(3), 290-296.
119. Rossoll, W.; Jablonka, S.; Andreassi, C.; Kroning, A.K.; Karle, K.; Monani, U.R.; Sendtner, M. Smn, the spinal muscular atrophy- Neuronal Death in Amyotrophic Lateral Sclerosis (ALS) determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J. Cell. Biol., 2003, 163(4), 801-812.
120. Monani, U.R. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron, 2005, 48(6), 885-896.
121. Zhang, Z.; Lotti, F.; Dittmar, K.; Younis, I.; Wan, L.; Kasim, M.; Dreyfuss, G. SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell, 2008, 133(4), 585-600.
122. Hua, Y.; Zhou, J. Survival motor neuron protein facilitates assembly of stress granules. FEBS Lett., 2004, 572(1-3), 69-74.
123. Bose, J.K.; Wang, I.F.; Hung, L.; Tarn, W.Y.; Shen, C.K. TDP-43 overexpression enhances exon-7 inclusion during SMN Pre-mRNA splicing. J. Biol. Chem., 2008, 283(43), 28852-28859.
124. Veldink, J.H.; van den Berg, L.H.; Cobben, J.M.; Stulp, R.P.; De Jong, J.M.; Vogels, O.J.; Baas, F.; Wokke, J.H.; Scheffer, H. Homozygous deletion of the survival motor neuron 2 gene is a prognostic factor in sporadic ALS. Neurology, 2001, 56(6), 749-752.
125. Veldink, J.H.; Kalmijn, S.; Van der Hout, A.H.; Lemmink, H.H.; Groeneveld, G.J.; Lummen, C.; Scheffer, H.; Wokke, J.H.; van den Berg, L.H. SMN genotypes producing less SMN protein increase susceptibility to and severity of sporadic ALS. Neurology, 2005, 65(6), 820-825.
126. Corcia, P.; Mayeux-Portas, V.; Khoris, J.; de Toffol, B.; Autret, A.; Müh, J.P.; Camu, W.; Andres, C. French ALS research group. amyotrophic lateral sclerosis: abnormal SMN1 gene copy number is a susceptibility factor for amyotrophic lateral sclerosis. Ann. Neurol., 2002, 51(2), 243-246.
127. Gavrilov, D.K.; Shi, X.; Das, K.; Gilliam, T.C.; Wang, C.H. Differential SMN2 expression associated with SMA severity. Nat. Genet., 1998, 20(3), 230-231.
128. Moulard, B.; Salachas, F.; Chassande, B.; Briolotti, V.; Meininger, V.; Malafosse, A.; Camu, W. Association between centromeric deletions of the SMN gene and sporadic adult-onset lower motor neuron disease. Ann. Neurol., 1998, 43(5), 640-644.
129. Gamez, J.; Barceló, M.J.; Muñoz, X.; Carmona, F.; Cuscó, I.; Baiget, M.; Cervera, C.; Tizzano, E.F. Survival and respiratory decline are not related to homozygous SMN2 deletions in ALS patients. Neurology, 2002, 59(9), 1456-1460.
130. Van Damme, P.; Dewil, M.; Robberecht, W.; Van Den, B.L. Excitotoxicity and amyotrophic lateral sclerosis. Neurodegener. Dis., 2005, 2(3-4), 147-159.
131. Aoki, M.; Lin, C.L.; Rothstein, J.D.; Geller, B.A.; Hosler, B.A.; Munsat, T.L.; Horvitz, H.R.; Brown, R.H., Jr. Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis. Ann. Neurol., 1998, 43(5), 645-653.
132. Trotti, D.; Aoki, M.; Pasinelli, P.; Berger, U.V.; Danbolt, N.C.; Brown, R.H., Jr.; Hediger, M.A. Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity. J. Biol. Chem., 2001, 276(1), 576-582.
133. Sabatelli, M.; Eusebi, F.; Al-Chalabi, A.; Conte, A.; Madia, F.; Luigetti, M.; Mancuso, I.; Limatola, C.; Trettel, F.; Sobrero, F.; Di Angelantonio, S.; Grassi, F.; Di Castro, A.; Moriconi, C.; Fucile, S.; Lattante, S.; Marangi, G.; Murdolo, M.; Orteschi, D.; Del Grande, A.; Tonali, P.; Neri, G.; Zollino, M. Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum. Mol. Genet., 2009, 18(20), 3997-4006.
134. Hervias, I.; Beal, M.F.; Manfredi, G. Mitochondrial dysfunction and amyotrophic lateral sclerosis. Muscle Nerve, 2006, 33(5), 598-608.
135. Comi, G.P.; Bordoni, A.; Salani, S.; Franceschina, L.; Sciacco, M.; Pelle, A.; Fortunato, F.; Zeviani, M.; Napoli, L.; Bresolin, N.; Moggio, M.; Ausenda, C.D.; Taanman, J.W.; Scarlato, G. Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann. Neurol., 1998, 43(1), 110-116.
136. Horner, R.D.; Kamins, K.G.; Feussner, J.R.; Grambow, S.C.; Hoff- Lindquist, J.; Harati, Y.; Mitsumoto, H.; Pascuzzi, R.; Spencer, P.S.; Tim, R.; Howard, D.; Smith, T.C.; Ryan, M.A.; Coffman, C.J.; Kasarskis, E.J. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology, 2003, 61(6), 742-749.
137. Wills, A.M.; Cronin, S.; Slowik, A.; Kasperaviciute, D.; Van Es, M.A.; Morahan, J.M.; Valdmanis, P.N.; Meininger, V.; Melki, J.; Shaw, C.E.; Rouleau, G.A.; Fisher, E.M.; Shaw, P.J.; Morrison, K.E.; Pamphlett, R.; Van den Berg, L.H.; Figlewicz, D.A.; Andersen, P.M.; Al-Chalabi, A.; Hardiman, O.; Purcell, S.; Landers, J.E.; Brown, R.H., Jr. A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS. Neurology, 2009, 73(1), 16-24.
138. Hosler, B.A.; Siddique, T.; Sapp, P.C.; Sailor, W.; Huang, M.C.; Hossain, A.; Daube, J.R.; Nance, M.; Fan, C.; Kaplan, J.; Hung, W.Y.; Kenna-Yasek, D.; Haines, J.L.; Pericak-Vance, M.A.; Horvitz, H.R., Brown, R.H., Jr. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA, 2000, 284(13), 1664-1669.
139. Morita, M.; Al-Chalabi, A.; Andersen, P.M.; Hosler, B.; Sapp, P.; Englund, E.; Mitchell, J.E.; Habgood, J.J.; de Belleroche, J.; Xi, J.; Jongjaroenprasert, W.; Horvitz, H.R.; Gunnarsson, L.G.; Brown, R.H. Jr. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology, 2006, 66(6), 839-844.
140. Vance, C.; Al-Chalabi, A.; Ruddy, D.; Smith, B.N.; Hu, X.; Sreedharan, J.; Siddique, T.; Schelhaas, H.J.; Kusters, B.; Troost, D.; Baas, F.; de Jong, V.; Shaw, C.E. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain, 2006, 129(Pt 4), 868-876.
141. Rusten, T.E.; Simonsen, A. ESCRT functions in autophagy and associated disease. Cell Cycle, 2008, 7, 1166-1172.
142. Parkinson, N.; Ince, P.G.; Smith, M.O.; Highley, R.; Skibinski, G.; Andersen, P.M.; Morrison, K.E.; Pall, H.S.; Hardiman, O.; Collinge, J.; Shaw, P.J.; Fisher, E.M. MRC Proteomics in ALS Study; FReJA Consortium. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology, 2006, 67, 1074-1077.
143. Blair, I.P.; Vance, C.; Durnall, J.C.; Williams, K.L.; Thoeng, A.; Shaw, C.E.; Nicholson, G.A. CHMP2B mutations are not a common cause of familial or sporadic amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry, 2008, 79(7), 849-850.
144. Schymick, J.C.; Yang, Y.; Andersen, P.M.; Vonsattel, J.P.; Greenway, M.; Momeni, P.; Elder, J.; Chiò, A.; Restagno, G.; Robberecht, W.; Dahlberg, C.; Mukherjee, O.; Goate, A.; Graff-Radford, N.; Caselli, R.J.; Hutton, M.; Gass, J.; Cannon, A.; Rademakers, R.; Singleton, A.B.; Hardiman, O.; Rothstein, J.; Hardy, J.; Traynor, B.J. Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes. J. Neurol. Neurosurg. Psychiatry, 2007, 78(7), 754-756.
145. Sleegers, K.; Brouwers, N.; Maurer-Stroh, S.; van Es, M.A.; Van Damme, P.; van Vught, P.W.; van der Zee, J.; Serneels, S.; De Pooter, T.; Van den Broeck, M.; Cruts, M.; Schymkowitz, J.; De Jonghe, P.; Rousseau, F.; van den Berg, L.H.; Robberecht, W.; Van Broeckhoven, C. Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology, 2008, 71(4), 253-259.