Roots to start research in amyotrophic lateral sclerosis: molecular pathways and novel therapeutics for future

References

Abe, K., Pan, L.-H., Watanabe, M., Kato, T., and Itoyama, Y. (1995). Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Neurosci. Lett. 199, 152–154.10.1016/0304-3940(95)12039-7Search in Google Scholar

Ackerley, S., Thornhill, P., Grierson, A.J., Brownlees, J., Anderton, B.H., Leigh, P.N., Shaw, C.E., and Miller, C.C.J. (2003). Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. J. Cell Biol. 161, 489–495.10.1083/jcb.200303138Search in Google Scholar PubMed PubMed Central

Aiden, H and Ralf, G. (2010). The impact of fingolimod (FTY720) in neuroimmunologic diseases: mechanisms beyond immunomodulation. Am J Pathol. J. 176, 2599–601.10.2353/ajpath.2010.100200Search in Google Scholar PubMed PubMed Central

Al-Chalabi, A., Andersen, P.M., Nilsson, P., Chioza, B., Andersson Jr, L., Russ, C., Shaw, C.E., Powell, J.F., and Leigh, P.N. (1999). Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum. Mol. Genet. 8, 157–164.10.1093/hmg/8.2.157Search in Google Scholar PubMed

Alexianu, M.E., Kozovska, M., and Appel, S.H. (2001). Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 57, 1282–1289.10.1212/WNL.57.7.1282Search in Google Scholar

Al-Saif, A., Al-Mohanna, F., and Bohlega, S. (2011). A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann. Neurol. 70, 913–919.10.1002/ana.22534Search in Google Scholar PubMed

An Open Label, Safety and Tolerability Continuation Study of Intracerebroventricular Administration of sNN0029 to Patients with Amyotrophic Lateral Sclerosis. https://clinicaltrials.gov/ct2/results?term=NCT01384162&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Anagnostou, G., Akbar, M.T., Paul, P., Angelinetta, C., Steiner, T.J., and de Belleroche, J. (2010). Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord. Neurobiol. Aging 31, 969–985.10.1016/j.neurobiolaging.2008.07.005Search in Google Scholar PubMed

Andersson, M.K., Ståhlberg, A., Arvidsson, Y., Olofsson, A., Semb, H., Stenman, G., Nilsson, O., and Pierre, A. (2008). The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol. 9, 37.10.1186/1471-2121-9-37Search in Google Scholar PubMed PubMed Central

Andrus, P.K., Fleck, T.J., Gurney, M.E., and Hall, E.D. (1998). Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 71, 2041–2048.10.1046/j.1471-4159.1998.71052041.xSearch in Google Scholar PubMed

Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., and Hashizume, Y. (2006). TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351, 602–611.10.1016/j.bbrc.2006.10.093Search in Google Scholar PubMed

Atassi, N., Cook, A., Pineda, C.M.E., Yerramilli-Rao, P., Pulley, D., and Cudkowicz, M. (2011). Depression in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 12, 109–112.10.3109/17482968.2010.536839Search in Google Scholar

Ayala, Y.M., Zago, P., D’Ambrogio, A., Xu, Y.-F., Petrucelli, L., Buratti, E., and Baralle, F.E. (2008). Structural determinants of the cellular localization and shuttling of TDP-43. J. Cell Sci. 121, 3778–3785.10.1242/jcs.038950Search in Google Scholar

Baines, C.P. (2010). Role of the mitochondrion in programmed necrosis. Front. Physiol. 1, 156.10.3389/fphys.2010.00156Search in Google Scholar

Bak, T.H. and Hodges, J.R. (2004). The effects of motor neurone disease on language: further evidence. Brain Lang. 89, 354–361.10.1016/S0093-934X(03)00357-2Search in Google Scholar

Baldwin, A.S. (2001). Series introduction: the transcription factor NF-κB and human disease. J. Clin. Invest. 107, 3–6.10.1172/JCI11891Search in Google Scholar PubMed PubMed Central

Bartholomãus, I., Kawakami, N., Odoardi, F., Schlãger, C., Miljkovic, D., Ellwart, J.W., Klinkert, W.E.F., Flügel-Koch, C., Issekutz, T.B., and Wekerle, H. (2009). Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462, 94–98.10.1038/nature08478Search in Google Scholar PubMed

Beal, M.F., Ferrante, R.J., Browne, S.E., Matthews, R.T., Kowall, N.W., and Brown, R.H. (1997). Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann. Neurol. 42, 644–654.10.1002/ana.410420416Search in Google Scholar PubMed

Beckman, J.S. and Koppenol, W.H. (1996). Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am. J. Physiol. Cell Physiol. 40, C1424.10.1152/ajpcell.1996.271.5.C1424Search in Google Scholar PubMed

Bensimon, G., Lacomblez, L., and Meininger, V. (1994). A controlled trial of riluzole in amyotrophic lateral sclerosis. N. Engl. J. Med. 330, 585–591.10.1056/NEJM199403033300901Search in Google Scholar PubMed

Blanquer, M., Pérez, E.M.A., Iniesta, F., Gómez, E.J., Meca, J., Villaverde, R., Izura, V., de Mingo, P., Martinez-Lage, J., and Martinez, S. (2010). Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: technical aspects and preliminary results from a clinical trial. Methods Findings Exp. Clin. Pharmacol. 32, 31–37.Search in Google Scholar

Blin, O., Azulay, J.P., Desnuelle, C., Bille-Turc, F., Braguer, D., Besse, D., Branger, E., Crevat, A., Serratrice, G., and Pouget, J.Y. (1996). A controlled one-year trial of dextromethorphan in amyotrophic lateral sclerosis. Clin. Neuropharmacol. 19, 189–192.10.1097/00002826-199619020-00009Search in Google Scholar PubMed

Block, M.L., Zecca, L., and Hong, J.-S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57–69.10.1038/nrn2038Search in Google Scholar

Borthwick, G.M., Johnson, M.A., Ince, P.G., Shaw, P.J., and Turnbull, D.M. (1999). Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann. Neurol. 46, 787–790.10.1002/1531-8249(199911)46:5<787::AID-ANA17>3.0.CO;2-8Search in Google Scholar

Brooks, B.R. (1994). El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J. Neurol. Sci. 124, 96–107.10.1016/0022-510X(94)90191-0Search in Google Scholar

Brooks, B.R., Miller, R.G., Swash, M., and Munsat, T.L. (2000). El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 1, 293–299.10.1080/146608200300079536Search in Google Scholar

Bruijn, L.I., Becher, M.W., Lee, M.K., Anderson, K.L., Jenkins, N.A., Copeland, N.G., Sisodia, S.S., Rothstein, J.D., Borchelt, D.R., and Price, D.L. (1997). ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18, 327–338.10.1016/S0896-6273(00)80272-XSearch in Google Scholar

Butcher, S.P. and Hamberger, A. (1987). In vivo studies on the extracellular, and veratrine-releasable, pools of endogenous amino acids in the rat striatum: effects of corticostriatal deafferentation and kainic acid lesion. J. Neurochem. 48, 713–721.10.1111/j.1471-4159.1987.tb05575.xSearch in Google Scholar

Byrne, S., Jordan, I., Elamin, M., and Hardiman, O. (2013). Age at onset of amyotrophic lateral sclerosis is proportional to life expectancy. Amyotrophic Lateral Sclerosis Frontotemporal Degener. 14, 604–607.10.3109/21678421.2013.809122Search in Google Scholar

Cassina, P., Cassina, A., Pehar, M., Castellanos, R., Gandelman, M., de León, A., Robinson, K.M., Mason, R.P., Beckman, J.S., and Barbeito, L. (2008). Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants. J. Neurosci. 28, 4115–4122.10.1523/JNEUROSCI.5308-07.2008Search in Google Scholar

Clinical Trial Ceftriaxone in Subjects With ALS. https://clinicaltrials.gov/ct2/results?term=NCT00349622&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Collard, J.F., Còté, F., and Julien, J.P. (1995). Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375, 61–64.10.1038/375061a0Search in Google Scholar

Corcoran, L.J., Mitchison, T.J., and Liu, Q. (2004). A novel action of histone deacetylase inhibitors in a protein aggresome disease model. Curr. Biol. 14, 488–492.10.1016/j.cub.2004.03.003Search in Google Scholar

Corrado, L., Del Bo, R., Castellotti, B., Ratti, A., Cereda, C., Penco, S., Sorarù, G., Carlomagno, Y., Ghezzi, S., and Pensato, V. (2010). Mutations of FUS gene in sporadic amyotrophic lateral sclerosis. Journal of medical genetics. 47, 190–194.10.1136/jmg.2009.071027Search in Google Scholar PubMed

Cox, P.A., Banack, S.A., and Murch, S.J. (2003). Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc. Natl. Acad. Sci. 100, 13380–13383.10.1073/pnas.2235808100Search in Google Scholar PubMed PubMed Central

Cozzolino, M. and Carri, M.T. (2012). Mitochondrial dysfunction in ALS. Prog. Neurobiol. 97, 54–66.10.1016/j.pneurobio.2011.06.003Search in Google Scholar PubMed

Crugnola, V., Lamperti, C., Lucchini, V., Ronchi, D., Peverelli, L., Prelle, A., Sciacco, M., Bordoni, A., Fassone, E., and Fortunato, F. (2010). Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis. Arch. Neurol. 67, 849–854.10.1001/archneurol.2010.128Search in Google Scholar PubMed

Cudkowicz, M.E., Shefner, J.M., Schoenfeld, D.A., Brown Jr, R.H., Johnson, H., Qureshi, M., Jacobs, M., Rothstein, J.D., Appel, S.H., and Pascuzzi, R.M. (2003). A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis. Neurology 61, 456–464.10.1212/WNL.61.4.456Search in Google Scholar

Cudkowicz, M.E., Shefner, J.M., Schoenfeld, D.A., Zhang, H., Andreasson, K.I., Rothstein, J.D., and Drachman, D.B. (2006). Trial of celecoxib in amyotrophic lateral sclerosis. Ann. Neurol. 60, 22–31.10.1002/ana.20903Search in Google Scholar PubMed

Cudkowicz, M.E., Andres, P.L., Macdonald, S.A., Bedlack, R.S., Choudry, R., Brown Jr, R.H., Zhang, H., Schoenfeld, D.A., Shefner, J., and Matson, S. (2009). Phase 2 study of sodium phenylbutyrate in ALS. Amyotroph. Lateral Scler. 10, 99–106.10.1080/17482960802320487Search in Google Scholar PubMed

Da Cruz, S. and Cleveland, D.W. (2011). Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr. Opin. Neurobiol. 21, 904–919.10.1016/j.conb.2011.05.029Search in Google Scholar PubMed PubMed Central

Daoud, H., Valdmanis, P.N., Kabashi, E., Dion, P., Dupre, N., Camu, W., Meininger, V., and Rouleau, G.A. (2009). Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J. Med. Genet. 46, 112–114.10.1136/jmg.2008.062463Search in Google Scholar PubMed

Davenport, R., Swingler, R., Chancellor, A., and Warlow, C. (1996). Avoiding false positive diagnoses of motor neuron disease: lessons from the Scottish Motor Neuron Disease Register. J. Neurol. Neurosurg. Psychiatry 60, 147–151.10.1136/jnnp.60.2.147Search in Google Scholar PubMed PubMed Central

David, A.S. and Gillham, R.A. (1986). Neuropsychological study of motor neuron disease. Psychosomatics 27, 441–445.10.1016/S0033-3182(86)72673-XSearch in Google Scholar

De Carvalho, M., Pinto, S., Costa, J., Evangelista, T., Ohana, B., and Pinto, A. (2010). A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 11, 456–460.10.3109/17482968.2010.498521Search in Google Scholar PubMed

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., and Adamson, J. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245–256.10.1016/j.neuron.2011.09.011Search in Google Scholar PubMed PubMed Central

Desnuelle, C., Dib, M., Garrel, C., and Favier, A. (2001). A double-blind, placebo-controlled randomized clinical trial of α-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 2, 9–18.10.1080/146608201300079364Search in Google Scholar PubMed

Drechsel, D.A., Estévez, A.G., Barbeito, L., and Beckman, J.S. (2012). Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS. Neurotoxicity Res. 22, 251–264.10.1007/s12640-012-9322-ySearch in Google Scholar PubMed PubMed Central

Dreyer, P., Lorenzen, C.Kr., Schou, L., and Felding, M. (2014). Survival in ALS with home mechanical ventilation non-invasively and invasively: a 15-year cohort study in west Denmark. Amyotrophic Lateral Sclerosis Frontotemporal Degener. 15, 62–67.10.3109/21678421.2013.837929Search in Google Scholar PubMed

Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS). https://clinicaltrials.gov/ct2/results?term=NCT00330681&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Farg, M.A., Sundaramoorthy, V., Sultana, J.M., Yang, S., Atkinson, R.A.K., Levina, V., Halloran, M.A., Gleeson, P.A., Blair, I.P., and Soo, KY. (2014). C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum. Mol. Genet. 23, 3579–3595.10.1093/hmg/ddu068Search in Google Scholar PubMed PubMed Central

Ferrante, R.J., Browne, S.E., Shinobu, L.A., Bowling, A.C., Baik, M.J., MacGarvey, U., Kowall, N.W., Brown, R.H., and Beal, M.F. (1997). Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J. Neurochem. 69, 2064–2074.10.1046/j.1471-4159.1997.69052064.xSearch in Google Scholar PubMed

Fitzmaurice, P., Shaw, I., Kleiner, H., Miller, R., Monks, T., Lau, S., Mitchell, J., and Lynch, P. (1996). Evidence for DNA damage in amyotrophic lateral sclerosis. Muscle Nerve 19, 797–798.Search in Google Scholar

Gallassi, R., Montagna, P., Ciardulli, C., Lorusso, S., Mussuto, V., and Stracciari, A. (1985). Cognitive impairment in motor neuron disease. Acta Neurol. Scand. 71, 480–484.10.1111/j.1600-0404.1985.tb03231.xSearch in Google Scholar PubMed

Galluzzi, L. and Kroemer, G. (2008). Necroptosis: a specialized pathway of programmed necrosis. Cell 135, 1161–1163.10.1016/j.cell.2008.12.004Search in Google Scholar PubMed

Gil, J., Funalot, B., Verschueren, A., Danel-Brunaud, V., Camu, W., Vandenberghe, N., Desnuelle, C., Guy, N., Camdessanche, J., and Cintas, P. (2008). Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study. Eur. J. Neurol. 15, 1245–1251.10.1111/j.1468-1331.2008.02307.xSearch in Google Scholar

Giordana, M.T., Piccinini, M., Grifoni, S., De Marco, G., Vercellino, M., Magistrello, M., Pellerino, A., Buccinnà, B., Lupino, E., and Rinaudo, M.T. (2010). TDP 43 Redistribution is an early event in sporadic amyotrophic lateral sclerosis. Brain Pathol. 20, 351–360.10.1111/j.1750-3639.2009.00284.xSearch in Google Scholar

Gordon, P.H., Doorish, C., Montes, J., Mosley, R.L., Diamond, B., Macarthur, R.B., Weimer, L.H., Kaufmann, P., Hays, A.P., and Rowland, L.P. (2006). Randomized controlled phase II trial of glatiramer acetate in ALS. Neurology 66, 1117–1119.10.1212/01.wnl.0000204235.81272.e2Search in Google Scholar

Gouveia, L.O. and De Carvalho, M. (2007). Young-onset sporadic amyotrophic lateral sclerosis: a distinct nosological entity? Amyotroph. Lateral Scler. 8, 323–327.10.1080/17482960701553956Search in Google Scholar

Gredal, O., Werdelin, L., Bak, S., Christensen, P.B., Boysen, G., Kristensen, M., Jespersen, J.H., Regeur, L., Hinge, H.H, and Jensen, T.S. (1997). A clinical trial of dextromethorphan in amyotrophic lateral sclerosis. Acta Neurol. Scand. 96, 8–13.10.1111/j.1600-0404.1997.tb00231.xSearch in Google Scholar

Hall, E.D., Oostveen, J.A., and Gurney, M.E. (1998). Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 23, 249–256.10.1002/(SICI)1098-1136(199807)23:3<249::AID-GLIA7>3.0.CO;2-#Search in Google Scholar

Halliwell, B. (2006). Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634–1658.10.1111/j.1471-4159.2006.03907.xSearch in Google Scholar

Harraz, M.M., Marden, J.J., Zhou, W., Zhang, Y., Williams, A., Sharov, V.S., Nelson, K., Luo, M., Paulson, H., and Schöneich, C. (2008). SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J. Clin. Invest. 118, 659.10.1172/JCI34060Search in Google Scholar

Hefferan, M.P., Johe, K., Hazel, T., Feldman, E.L., Lunn, J.S., and Marsala, M. (2011). Optimization of immunosuppressive therapy for spinal grafting of human spinal stem cells in a rat model of ALS. Cell Transplant. 20, 1153–1161.10.3727/096368910X564553Search in Google Scholar

Henkel, J.S., Beers, D.R., Zhao, W., and Appel, S.H. (2009). Microglia in ALS: the good, the bad, and the resting. J. Neuroimmune Pharmacol. 4, 389–398.10.1007/s11481-009-9171-5Search in Google Scholar

Hewitt, C., Kirby, J., Highley, J.R., Hartley, J.A., Hibberd, R., Hollinger, H.C., Williams, T.L., Ince, P.G., McDermott, C.J., and Shaw, P.J. (2010). Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis. Arch. Neurol. 67, 455–461.10.1001/archneurol.2010.52Search in Google Scholar

Imitola, J., Raddassi, K., Park, K.I., Mueller, F.-J., Nieto, M., Teng, Y.D., Frenkel, D., Li, J., Sidman, R.L., and Walsh, C.A. (2004). Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway. Proc. Natl. Acad. Sci. 101, 18117–18122.10.1073/pnas.0408258102Search in Google Scholar

Ince, P.G., Shaw, P.J., Slade, J.Y., Jones, C., and Hudgson, P. (1996). Familial amyotrophic lateral sclerosis with a mutation in exon 4 of the Cu/Zn superoxide dismutase gene: pathological and immunocytochemical changes. Acta Neuropathol. 92, 395–403.10.1007/s004010050535Search in Google Scholar

Jokic, N., Gonzalez de Aguilar, J.L., Dimou, L., Lin, S., Fergani, A., Ruegg, M.A., Schwab, M.E., Dupuis, L., and Loeffler, J.P. (2006). The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model. EMBO Rep. 7, 1162–1167.10.1038/sj.embor.7400826Search in Google Scholar

Kabashi, E., Valdmanis, P.N., Dion, P., Spiegelman, D., McConkey, B.J., Velde, C.V., Bouchard, J.-P., Lacomblez, L., Pochigaeva, K., and Salachas, F. (2008). TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572–574.10.1038/ng.132Search in Google Scholar

Kalmar, B., Novoselov, S., Gray, A., Cheetham, M.E., Margulis, B., and Greensmith, L. (2008). Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1G93A mouse model of ALS. J. Neurochem. 107, 339–350.10.1111/j.1471-4159.2008.05595.xSearch in Google Scholar

Kalra, S., Cashman, N.R., Caramanos, Z., Genge, A., and Arnold, D.L. (2003). Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. Am. J. Neuroradiol. 24, 476–480.Search in Google Scholar

Kaltschmidt, C., Kaltschmidt, B., Lannes-Vieira, J., Kreutzberg, G.W., Wekerle, H., Baeuerle, P.A., and Gehrmann, J. (1994). Transcription factor NF-κB is activated in microglia during experimental autoimmune encephalomyelitis. J. Neuroimmunol. 55, 99–106.10.1016/0165-5728(94)90151-1Search in Google Scholar

Karussis, D., Karageorgiou, C., Vaknin-Dembinsky, A., Gowda-Kurkalli, B., Gomori, J.M., Kassis, I., Bulte, J.W.M., Petrou, P., Ben-Hur, T., and Abramsky, O. (2010). Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch. Neurol. 67, 1187–1194.10.1001/archneurol.2010.248Search in Google Scholar

Kasarskis, E.J., Scarlata, D., Hill, R., Fuller, C., Stambler, N., and Cedarbaum, J.M. (1999). A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials. J. Neurol. Sci. 169, 118–125.10.1016/S0022-510X(99)00230-0Search in Google Scholar

Kaufmann, P., Thompson, J.L.P, Levy, G., Buchsbaum, R., Shefner, J., Krivickas, L.S., Katz, J., Rollins, Y., Barohn, R.J., and Jackson, C.E. (2009). Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann. Neurol. 66, 235–244.10.1002/ana.21743Search in Google Scholar PubMed PubMed Central

Kawamata, H. and Manfredi, G. (2008). Different regulation of wild-type and mutant Cu, Zn superoxide dismutase localization in mammalian mitochondria. Hum. Mol. Genet. 17, 3303–3317.10.1093/hmg/ddn226Search in Google Scholar PubMed PubMed Central

Kew, J.J.M., Goldstein, L.H., Leigh, P.N., Abrahams, S., Cosgrave, N., Passingham, R.E., Frackowiak, R.S.J., and Brooks, D.J. (1993).The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis A neuropsychological and positron emission tomography study. Brain 116, 1399–1423.10.1093/brain/116.6.1399Search in Google Scholar PubMed

Kiaei, M., Kipiani, K., Petri, S., Chen, J., Calingasan, N.Y., and Beal, M.F. (2006). Celastrol blocks neuronal cell death and extends life in transgenic mouse model of amyotrophic lateral sclerosis. Neurodegener. Dis. 2, 246–254.10.1159/000090364Search in Google Scholar PubMed

Kong, J. and Xu, Z. (1998). Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J. Neurosci. 18, 3241–3250.10.1523/JNEUROSCI.18-09-03241.1998Search in Google Scholar

Kruman, I.I., Pedersen, W.A., Springer, J.E., and Mattson, M.P. (1999). ALS-linked Cu/Zn-OD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis. Exp. Neurol. 160, 28–39.10.1006/exnr.1999.7190Search in Google Scholar PubMed

Kwiatkowski Jr., T., Bosco, D.A., Leclerc, A.L., Tamrazian, E., Vanderburg, C.R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E.J., and Munsat, T. (2009). Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205–1208.10.1126/science.1166066Search in Google Scholar PubMed

Lecht, S., Haroutiunian, S., Hoffman, A., and Lazarovici, P. (2007). Rasagiline –a novel MAO B inhibitor in Parkinson’s disease therapy. Ther. Clin. Risk Manage. 3, 467.Search in Google Scholar

Lee, J., Ryu, H., and Kowall, N.W. (2009). Motor neuronal protection by L-arginine prolongs survival of mutant SOD1 (G93A) ALS mice. Biochem. Biophys. Res. Commun. 384, 524–529.10.1016/j.bbrc.2009.05.015Search in Google Scholar PubMed PubMed Central

Levy, G., Kaufmann, P., Buchsbaum, R., Montes, J., Barsdorf, A., Arbing, R., Battista, V., Zhou, X., Mitsumoto, H., and Levin, B. (2006). A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS. Neurology 66, 660–663.10.1212/01.wnl.0000201182.60750.66Search in Google Scholar PubMed

Lewis, C.-A., Manning, J., Rossi, F., and Krieger, C. (2012). The neuroinflammatory response in ALS: the roles of microglia and T cells. Neurol. Res. Int. http://dx.doi.org/10.1155/2012/803701.10.1155/2012/803701Search in Google Scholar PubMed PubMed Central

Li, Y., Ray, P., Rao, E.J., Shi, C., Guo, W., Chen, X., Woodruff, E.A., Fushimi, K., and Wu, J.Y. (2010). A Drosophila model for TDP-43 proteinopathy. Proc. Natl. Acad. Sci. 107, 3169–3174.10.1073/pnas.0913602107Search in Google Scholar PubMed PubMed Central

Lin, M.T. and Beal, M.F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443, 787–795.10.1038/nature05292Search in Google Scholar

Lin, C.-L.G., Bristol, L.A., Jin, L., Dykes-Hoberg, M., Crawford, T., Clawson, L., and Rothstein, J.D. (1998). Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron 20, 589–602.10.1016/S0896-6273(00)80997-6Search in Google Scholar

Liu, R., Althaus, J.S., Ellerbrock, B.R., Becker, D.A., and Gurney, M.E. (1998). Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann. Neurol. 44, 763–770.10.1002/ana.410440510Search in Google Scholar PubMed

Liu, D., Wen, J., Liu, J., and Li, L. (1999). The roles of free radicals in amyotrophic lateral sclerosis: reactive oxygen species and elevated oxidation of protein, DNA, and membrane phospholipids. FASEB J. 13, 2318–2328.10.1096/fasebj.13.15.2318Search in Google Scholar PubMed

Logroscino, G., Traynor, B., Hardiman, O., Couratier, P., Mitchell, J., Swingler, R., and Beghi, E. (2008). Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J. Neurol. Neurosurg. Psychiatry 79, 6–11.10.1136/jnnp.2006.104828Search in Google Scholar PubMed

Lomen-Hoerth, C., Murphy, J., Langmore, S., Kramer, J.H., Olney, R.K., and Miller, B. (2003). Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60, 1094–1097.10.1212/01.WNL.0000055861.95202.8DSearch in Google Scholar PubMed

Lou, J.-S., Reeves, A., Benice, T., and Sexton, G. (2003). Fatigue and depression are associated with poor quality of life in ALS. Neurology 60, 122–123.10.1212/01.WNL.0000042781.22278.0ASearch in Google Scholar PubMed

Louwerse, E.S., Weverling, G.J., Bossuyt, P.M.M., Meyjes, F.E.P., and de Jong, J.M.B.V. (1995). Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch. Neurol. 52, 559–564.10.1001/archneur.1995.00540300031009Search in Google Scholar PubMed

Mackenzie, I.R.A., Bigio, E.H., Ince, P.G., Geser, F., Neumann, M., Cairns, N.J., Kwong, L.K., Forman, M.S., Ravits, J., and Stewart, H. (2007). Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann. Neurol. 61, 427–434.10.1002/ana.21147Search in Google Scholar PubMed

Manfredi, G. and Xu, Z. (2005). Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. Mitochondrion 5, 77–87.10.1016/j.mito.2005.01.002Search in Google Scholar PubMed

Matloubian, M., Lo, C.G., Cinamon, G., Lesneski, M.J., Xu, Y., Brinkmann, V., Allende, M.L., Proia, R.L., and Cyster JG. (2004). Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360.10.1038/nature02284Search in Google Scholar PubMed

Mazzini, L., Mareschi, K., Ferrero, I., Vassallo, E., Oliveri, G., Nasuelli, N., Oggioni, G.D., Testa, L., and Fagioli, F. (2008). Stem cell treatment in amyotrophic lateral sclerosis. J. Neurol. Sci. 265, 78–83.10.1016/j.jns.2007.05.016Search in Google Scholar PubMed

Meininger, V., Bensimon, G., Bradley, W.G., Brooks, B.R., Douillet, P., Eisen, A.A., Lacomblez, L., Nigel Leigh, P., and Robberecht, W. (2004). Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials. Amyotroph. Lateral Scler. 5, 107–117.10.1080/14660820410019602Search in Google Scholar PubMed

Miciak, J.J., Warsing, L.C., Tibbs, M.E., Jasper, J.R., Jampel, S.B., Malik, F.I., Tankersley, C., and Wagner, K.R. (2013). Fast skeletal muscle troponin activator in the dy2J muscular dystrophy model. Muscle Nerve 48, 279–285.10.1002/mus.23848Search in Google Scholar PubMed

Miller, R.G., Petajan, J.H., Bryan, W.W., Armon, C., Barohn, R.J., Goodpasture, J.C., Hoagland, R.J., Parry, G.J., Ross, M.A., and Stromatt, S.C. (1996). A placebo controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. Ann. Neurol. 39, 256–260.10.1002/ana.410390215Search in Google Scholar PubMed

Miller, R.G., Moore 2nd, D.H., Gelinas, D.F., Dronsky, V., Mendoza, M., Barohn, R.J., Bryan, W., Ravits, J., Yuen, E., and Neville, H. (2001). Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 56, 843–848.10.1212/WNL.56.7.843Search in Google Scholar

Mori, K., Arzberger, T., Grãsser, F.A., Gijselinck, I., May, S., Rentzsch, K., Weng, S.-M., Schludi, M.H., van der Zee, J., and Cruts, M.(2013). Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol. 126, 881–893.10.1007/s00401-013-1189-3Search in Google Scholar PubMed

Murphy, J., Henry, R., and Lomen-Hoerth, C. (2007). Establishing subtypes of the continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch. Neurol. 64, 330–334.10.1001/archneur.64.3.330Search in Google Scholar PubMed

N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder. https://clinicaltrials.gov/ct2/results?term=NCT00539513&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Neary, D., Snowden, J.S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P.H., and Albert, M. (1998). Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51, 1546–1554.10.1212/WNL.51.6.1546Search in Google Scholar

Neumann, M., Sampathu, D.M., Kwong, L.K., Truax, A.C., Micsenyi, M.C., Chou, T.T., Bruce, J., Schuck, T., Grossman, M., and Clark, C.M. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133.10.1126/science.1134108Search in Google Scholar PubMed

Placebo Controlled Study of ONO2506PO in the Presence of Riluzole in Patients With Amyotrophic Lateral Sclerosis (ALS). https://clinicaltrials.gov/ct2/results?term=NCT00403104&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Puls, I., Jonnakuty, C., LaMonte, B.H., Holzbaur, E.L.F, Tokito, M., Mann, E., Floeter, M.K., Bidus, K., Drayna, D., and Oh, S.J. (2003). Mutant dynactin in motor neuron disease. Nat. Genet. 33, 455–456.10.1038/ng1123Search in Google Scholar

Radunovic, A., Annane, D., Jewitt, K., and Mustfa, N. (2009). Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 7, CD004427.10.1002/14651858.CD004427.pub2Search in Google Scholar

Rakowicz, W.P. and Hodges, J.R. (1998). Dementia and aphasia in motor neuron disease: an underrecognised association? J. Neurol. Neurosurg. Psychiatry 65, 881–889.10.1136/jnnp.65.6.881Search in Google Scholar

Renton, A.E., Majounie, E., Waite, A., Simón-Sànchez, J., Rollinson, S., Gibbs, J.R., Schymick, J.C., Laaksovirta, H., Van Swieten, J.C., and Myllykangas, L. (2011). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257–268.10.1016/j.neuron.2011.09.010Search in Google Scholar

Riddoch-Contreras, J., Yang, S.-Y., Dick, J.R.T., Goldspink, G., Orrell, R.W., and Greensmith, L. (2009). Mechano-growth factor, an IGF-I splice variant, rescues motoneurons and improves muscle function in SOD1^G93A mice. Exp. Neurol. 215, 281–289.10.1016/j.expneurol.2008.10.014Search in Google Scholar

Rosenfeld, J., King, R.M., Jackson, C.E., Bedlack, R.S., Barohn, R.J., Dick, A., Phillips, L.H., Chapin, J., Gelinas, D.F., and Lou, J.-S. (2008). Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Amyotroph. Lateral Scler. 9, 266–272.10.1080/17482960802028890Search in Google Scholar

Ross, C.A. and Poirier, M.A. (2004). Protein aggregation and neurodegenerative disease. Nat. Med. 10, S10–S17.10.1038/nm1066Search in Google Scholar

Rothstein, J.D. (1994). Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clin. Neurosci. 3, 348–359.Search in Google Scholar

Rothstein, J.D., Tsai, G., Kuncl, R.W., Clawson, L., Cornblath, D.R., Drachman, D.B., Pestronk, A., Stauch, B.L., and Coyle, J.T. (1990). Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann. Neurol. 28, 18–25.10.1002/ana.410280106Search in Google Scholar

Rothstein, J.D., Dykes-Hoberg, M., Pardo, C.A., Bristol, L.A., Jin, L., Kuncl, R.W., Kanai, Y., Hediger, M.A., Wang, Y., and Schielke, J.P. (1996). Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16, 675–686.10.1016/S0896-6273(00)80086-0Search in Google Scholar

Rowland, L.P. and Shneider, N.A. (2001). Amyotrophic lateral sclerosis. N. Engl. J. Med. 344, 1688–1700.10.1056/NEJM200105313442207Search in Google Scholar PubMed

Rudnicki, S., Berry, J., Ingersoll, E., Archibald, D., Cudkowicz, M., Kerr, D., and Dong, Y.(2013). Dexpramipexole effects on functional decline in ALS patients in a phase II study: subgroup analysis of demographic and clinical characteristics. Neurology 4, 149.Search in Google Scholar

Rutherford, N.J., Zhang, Y.-J., Baker, M., Gass, J.M., Finch, N.A., Xu, Y.-F., Stewart. H., Kelley. B.J., Kuntz, K., and Crook, R.J.P. (2008). Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet. 4, e1000193.10.1371/journal.pgen.1000193Search in Google Scholar

Ryberg, H., Askmark, H., and Persson, L.I. (2003). A double-blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid levels and clinical parameters. Acta Neurol. Scand. 108, 1–8.10.1034/j.1600-0404.2003.00111.xSearch in Google Scholar

Safety and Tolerability of Anakinra in Combination With Riluzol in Amyotrophic Lateral Sclerosis. https://clinicaltrials.gov/ct2/results?term=NCT01277315&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Safety Extension Study of TRO19622 in ALS. https://clinicaltrials.gov/ct2/results?term=NCT01285583&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Safety Study of High Doses of Zinc in ALS Patients. https://clinicaltrials.gov/ct2/results?term=NCT01259050&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Said Ahmed, M., Hung, W.-Y., Zu, J.S., Hockberger, P., and Siddique, T. (2000). Increased reactive oxygen species in familial amyotrophic lateral sclerosis with mutations in SOD1. J. Neurol. Sci. 176, 88–94.10.1016/S0022-510X(00)00317-8Search in Google Scholar

Santa-Cruz, L.D., Ramírez-Jarquín, U.N., and Tapia, R. (2012). Role of mitochondrial dysfunction in motor neuron degeneration in ALS. Amyotroph. Lateral Scler. 197–224.Search in Google Scholar

Sargsyan, S.A., Monk, P.N., and Shaw, P.J. (2005). Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis. Glia 51, 241–253.10.1002/glia.20210Search in Google Scholar PubMed

Sasika, S. and Iwata, M. (2007). Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 66, 10–16.10.1097/nen.0b013e31802c396bSearch in Google Scholar PubMed

Schwartz, J.H. (1979). Axonal transport: components, mechanisms, and specificity. Ann. Rev. Neurosci. 2, 467–504.10.1146/annurev.ne.02.030179.002343Search in Google Scholar PubMed

Sen, I., Nalini, A., Joshi, N.B., and Joshi, P.G. (2005). Cerebrospinal fluid from amyotrophic lateral sclerosis patients preferentially elevates intracellular calcium and toxicity in motor neurons via AMPA/kainate receptor. J. Neurol. Sci. 235, 45–54.10.1016/j.jns.2005.03.049Search in Google Scholar PubMed

Shaw, P.J. (2005). Molecular and cellular pathways of neurodegeneration in motor neurone disease. J. Neurol. Neurosurg. Psychiatry 76, 1046–1057.10.1136/jnnp.2004.048652Search in Google Scholar PubMed PubMed Central

Shefner, J.M., Cudkowicz, M.E., Schoenfeld, D., Conrad, T., Taft, J., Chilton, M., Urbinelli, L., Qureshi, M., Zhang, H., and Pestronk, A. (2004). A clinical trial of creatine in ALS. Neurology 63, 1656–1661.10.1212/01.WNL.0000142992.81995.F0Search in Google Scholar PubMed

Sheng, Y., Chattopadhyay, M., Whitelegge, J., and Selverstone Valentine, J. (2012). SOD1 aggregation and ALS: role of metallation states and disulfide status. Curr. Top. Med. Chem. 12, 2560–2572.10.2174/1568026611212220010Search in Google Scholar PubMed

Shoemaker, J.L., Seely, K.A., Reed, R.L., Crow, J.P., and Prather, P.L. (2007). The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J. Neurochem. 101, 87–98.10.1111/j.1471-4159.2006.04346.xSearch in Google Scholar

Siciliano, G., D’Avino, C., Corona, A.D., Barsacchi, R., Kusmic, C., Rocchi, A., Pastorini, E., and Murri, L. (2002). Impaired oxidative metabolism and lipid peroxidation in exercising muscle from ALS patients. Amyotroph. Lateral Scler. 3, 57–62.10.1080/146608202760196011Search in Google Scholar

Sorenson, E.J., Windbank, A.J., Mandrekar, J.N., Bamlet, W.R., Appel, S.H., Armon, C., Barkhaus, P.E., Bosch, P., Boylan, K., and David, W.S. (2008). Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology 71, 1770–1775.10.1212/01.wnl.0000335970.78664.36Search in Google Scholar

Spataro, R., Lo Re, M., Piccoli, T., Piccoli, F., and La Bella, V. (2010). Causes and place of death in Italian patients with amyotrophic lateral sclerosis. Acta Neurol. Scand. 122, 217–223.10.1111/j.1600-0404.2009.01290.xSearch in Google Scholar

Sreedharan, J., Blair, I.P., Tripathi, V.B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J.C., Williams, K.L., and Buratti, E. (2008). TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668–1672.10.1126/science.1154584Search in Google Scholar

Stommel, E.W., Cohen, J.A., Fadul, C.E., Cogbill, C.H., Graber, D.J., Kingman, L., Mackenzie, T., Channon Smith, J.Y., and Harris, B.T. (2009). Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial. Amyotroph. Lateral Scler. 10, 393–404.10.3109/17482960802709416Search in Google Scholar

Strong, M.J. (2001). Progress in clinical neurosciences: the evidence for ALS as a multisystems disorder of limited phenotypic expression. Can. J. Neurol. Sci. 28, 283–298.10.1017/S0317167100001505Search in Google Scholar

Strong, M.J., Grace, G.M., Orange, J.B., Leeper, H.A., Menon, R.S., and Aere, C. (1999). A prospective study of cognitive impairment in ALS. Neurology 53, 1665–1665.10.1212/WNL.53.8.1665Search in Google Scholar

Synofzik, M., Maetzler, W., Grehl, T., Prudlo, J., vom Hagen, J.M.L., Haack, T., Rebassoo, P., Munz, M., Schöls, L., and Biskup, S. (2012). Screening in ALS and FTD patients reveals 3 novel UBQLN2 mutations outside the PXX domain and a pure FTD phenotype. Neurobiol. Aging 33, 2949.e2913–2949.e2917.10.1016/j.neurobiolaging.2012.07.002Search in Google Scholar

SZi, S. and Iwata, M. (1996). Ultrastructural study of synapses in the anterior horn neurons of patients with amyotrophic lateral sclerosis. Neurosci. Lett. 204, 53–56.10.1016/0304-3940(96)12314-4Search in Google Scholar

Takata, M., Tanaka, H., Kimura, M., Nagahara, Y., Tanaka, K., Kawasaki, K., Seto, M., Tsuruma, K., Shimazawa, M., and Hara, H. (2013). Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis. Br. J. Pharmacol. 170, 341–351.10.1111/bph.12277Search in Google Scholar PubMed PubMed Central

Talampanel for Amyotrophic Lateral Sclerosis (ALS). https://clinicaltrials.gov/ct2/results?term=NCT00696332&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Tateishi, T., Hokonohara, T., Yamasaki, R., Miura, S., Kikuchi, H., Iwaki, A., Tashiro, H., Furuya, H., Nagara, Y., and Ohyagi, Y. (2009). Multiple system degeneration with basophilic inclusions in Japanese ALS patients with FUS mutation. Acta Neuropathol. 119, 335–364.Search in Google Scholar

Tatom, J.B., Wang, D.B., Dayton, R.D., Skalli, O., Hutton, M.L., Dickson, D.W., and Klein, R.L. (2009). Mimicking aspects of frontotemporal lobar degeneration and Lou Gehrig’s disease in rats via TDP-43 overexpression. Mol. Ther. 17, 607–613.10.1038/mt.2009.3Search in Google Scholar PubMed PubMed Central

The Effect of GCSF in the Treatment of ALS Patients. https://clinicaltrials.gov/ct2/results?term=NCT01825551&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Ticozzi, N., Tiloca, C., Morelli, C., Colombrita, C., Poletti, B., Doretti, A., Maderna, L., Messina, S., Ratti, A., and Silani, V. (2011). Genetics of familial amyotrophic lateral sclerosis. Arch. Ital. Biol. 149, 65–82.Search in Google Scholar

Tomkins, J., Usher, P., Slade, J.Y., Ince, P.G., Curtis, A., Bushby, K., and Shaw, P.J. (1998). Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9, 3967–3970.10.1097/00001756-199812010-00036Search in Google Scholar PubMed

Tönges, L., Günther, R., Suhr, M., Jansen, J., Balck, A., Saal, K.A., Barski, E., Nientied, T., Götz, A.A., and Koch, J.C. (2014). Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis. Glia 62, 217–232.10.1002/glia.22601Search in Google Scholar PubMed

Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis. https://clinicaltrials.gov/ct2/results?term=NCT00136110&Search=Search. Accessed May 6, 2014.Search in Google Scholar

Turner, M., Parton, M., Shaw, C., Leigh, P., and Al-Chalabi, A. (2003). Prolonged survival in motor neuron disease: a descriptive study of the King’s database 1990–2002. J. Neurol. Neurosurg. Psychiatry 74, 995–997.10.1136/jnnp.74.7.995Search in Google Scholar PubMed PubMed Central

Turner, M.R., Cagnin, A., Turkheimer, F.E., Miller, C.C.J., Shaw, C.E., Brooks, D.J., Leigh, P.N., and Banati, R.B. (2004). Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [¹¹C](R)-PK11195 positron emission tomography study. Neurobiol. Dis. 15, 601–609.10.1016/j.nbd.2003.12.012Search in Google Scholar PubMed

Uccelli, A., Milanese, M., Principato, M.C., Morando, S., Bonifacino, T., Vergani, L., Giunti, D., Voci, A., Carminati, E., and Giribaldi, F. (2012). Intravenous mesenchymal stem cells improve survival and motor function in experimental amyotrophic lateral sclerosis. Mol. Med. 18, 794.10.2119/molmed.2011.00498Search in Google Scholar PubMed PubMed Central

Vance, C., Rogelj, B., Hortobágyi, T., De Vos, K.J., Nishimura, A.L., Sreedharan, J., Hu, X., Smith, B., Ruddy, D., and Wright, P. (2009). Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208–1211.10.1126/science.1165942Search in Google Scholar PubMed PubMed Central

Vielhaber, S., Kunz, D., Winkler, K., Wiedemann, F.R., Kirches, E., Feistner, H., Heinze, H.-J., Elger, C.E., Schubert, W., and Kunz, W.S. (2000). Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. Brain 123, 1339–1348.10.1093/brain/123.7.1339Search in Google Scholar PubMed

Waibel, S., Reuter, A., Malessa, S., Blaugrund, E., and Ludolph, A.C. (2004). Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. J. Neurol. 251, 1080–1084.10.1007/s00415-004-0481-5Search in Google Scholar PubMed

Wang, H., O’Reilly, É.J., Weisskopf, M.G., Logroscino, G., McCullough, M.L., Schatzkin, A., Kolonel, L.N., and Ascherio, A. (2011). Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies. American journal of epidemiology. 173, 595–602.10.1093/aje/kwq416Search in Google Scholar PubMed PubMed Central

Weishaupt, J.H., Bartels, C., Pölking, E., Dietrich, J., Rohde, G., Poeggeler, B., Mertens, N., Sperling, S., Bohn, M., and Hüther, G. (2006). Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J. Pineal Res. 41, 313–323.10.1111/j.1600-079X.2006.00377.xSearch in Google Scholar PubMed

Weydt, P., Hong, S., Witting, A., Möller, T., Stella, N., and Kliot, M. (2005). Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotroph. Lateral Scler. 6, 182–184.10.1080/14660820510030149Search in Google Scholar PubMed

Wiedemann, F.R., Manfredi, G., Mawrin, C., Beal, M.F., and Schon, E.A. (2002). Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J. Neurochem. 80, 616–625.10.1046/j.0022-3042.2001.00731.xSearch in Google Scholar PubMed

Williams, K.L., Fifita, J.A., Vucic, S., Durnall, J.C., Kiernan, M.C., Blair, I.P., and Nicholson, G.A. (2013). Pathophysiological insights into ALS with C9ORF72 expansions. J. Neurol. Neurosurg. Psychiatry 84, 931–935.10.1136/jnnp-2012-304529Search in Google Scholar PubMed

Williamson, T.L. and Cleveland, D.W. (1999). Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat. Neurosci. 2, 50–56.10.1038/4553Search in Google Scholar PubMed

Wils, H., Kleinberger, G., Janssens, J., Pereson, S., Joris, G., Cuijt, I., Smits, V., Ceuterick-de Groote, C., Van Broeckhoven, C., and Kumar-Singh, S. (2010). TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc. Natl. Acad. Sci. 107, 3858–3863.10.1073/pnas.0912417107Search in Google Scholar PubMed PubMed Central

Xie, Y., Weydt, P., Howland, D.S., Kliot, M., and Möller, T. (2004). Inflammatory mediators and growth factors in the spinal cord of G93A SOD1 rats. Neuroreport 15, 2513–2516.10.1097/00001756-200411150-00016Search in Google Scholar PubMed

Xu, L., Yan, J., Chen, D., Welsh, A.M., Hazel, T., Johe, K., Hatfield, G., and Koliatsos, V.E. (2006a). Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation 82, 865–875.10.1097/01.tp.0000235532.00920.7aSearch in Google Scholar PubMed

Xu, Z., Chen, S., Li, X., Luo, G., Li, L., and Le, W. (2006b). Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis. Neurochem. Res. 31, 1263–1269.10.1007/s11064-006-9166-zSearch in Google Scholar PubMed

Yan, J., Xu, L., Welsh, A.M., Hatfield, G., Hazel, T., Johe, K., and Koliatsos, V.E. (2007). Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord. PLoS Med. 4, e39.10.1371/journal.pmed.0040039Search in Google Scholar PubMed PubMed Central

Ying, H. and Yue, B.Y.J.T. (2012). Cellular and molecular biology of optineurin. Int. Rev. Cell Mol. Biol. 294, 223–258.10.1016/B978-0-12-394305-7.00005-7Search in Google Scholar PubMed PubMed Central