Biomarkers and future targets for development in amyotrophic lateral sclerosis

Current Medicinal Chemistry

Volumn 21, Issue 31, 2014, Pages 3535-3550

  Menon, Parvathi ^a   Kiernan, Matthew C ^b   Vucic, Steve ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Amyotrophic lateral sclerosis; Clinical trial; Excitotoxicity; Glutamate; Motor neuron disease; Riluzole

Indexed keywords

AMPA RECEPTOR; ANTIARRHYTHMIC AGENT; ANTICONVULSIVE AGENT; ANTISENSE OLIGONUCLEOTIDE; BIOLOGICAL MARKER; CARBAMAZEPINE; COPPER ZINC SUPEROXIDE DISMUTASE; DEXPRAMIPEXOLE; DNA BINDING PROTEIN; EXCITATORY AMINO ACID TRANSPORTER 2; FLECAINIDE; FUSED IN SARCOMA PROTEIN; GLUTAMIC ACID; HEXANUCLEOTIDE; KAINIC ACID RECEPTOR; LAMOTRIGINE; MEXILETINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NUCLEOTIDE; PHENYTOIN; RILUZOLE; SODIUM ION; TRANSACTIVE REGION DNA BINDING PROTEIN; UNCLASSIFIED DRUG; NEUROPROTECTIVE AGENT; SODIUM CHANNEL; SUPEROXIDE DISMUTASE;

AMYOTROPHIC LATERAL SCLEROSIS; ANTISENSE THERAPY; ARTICLE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG DESIGN; DRUG EFFICACY; EXCITOTOXICITY; GENE EXPRESSION; GENE MUTATION; GENETIC ASSOCIATION; HEREDITY; HUMAN; HYPOTHESIS; MEMBRANE DEPOLARIZATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MOTONEURON; MULTICENTER STUDY (TOPIC); NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; NUCLEOTIDE REPEAT; OPEN READING FRAME; OXIDATIVE STRESS; PATHOGENESIS; PATHOPHYSIOLOGY; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); SODIUM CONDUCTANCE; ANIMAL; CHEMISTRY; DISEASE MODEL; GENETICS; METABOLISM; PATHOLOGY;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BIOLOGICAL MARKERS; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; GLUTAMIC ACID; HUMANS; NEUROPROTECTIVE AGENTS; OLIGONUCLEOTIDES, ANTISENSE; RECEPTORS, AMPA; SODIUM CHANNELS; SUPEROXIDE DISMUTASE;

EID: 84929082312     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867321666140601161148     Document Type: Article

References (268)

1. Kiernan, M. C.; Vucic, S.; Cheah, B. C.; Turner, M. R.; Eisen, A.; Hardiman, O.; Burrell, J. R.; Zoing, M. C. Amyotrophic lateral sclerosis. Lancet, 2011, 377, 942-955.
2. Gros-Louis, F.; Gaspar, C.; Rouleau, G. A. Genetics of familial and sporadic amyotrophic lateral sclerosis. Biochim. Biophys. Acta, 2006, 1762, 956-972.
3. Pasinelli, P.; Brown, R. H. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci., 2006, 7, 710-723.
4. Patel, S. A.; Maragakis, N. J. Amyotrophic lateral sclerosis: pathogenesis, differential diagnoses, and potential interventions. J. Spinal Cord Med., 2002, 25, 262-273.
5. Neusch, C.; Bahr, M.; Schneider-Gold, C. Glia cells in amyotrophic lateral sclerosis: new clues to understanding an old disease? Muscle Nerve, 2007, 35, 712-724.
6. Gonzalez De Aguilar, J. L.; Echaniz-Laguna, A.; Fergani, A.; Rene, F.; Meininger, V.; Loeffler, J. P.; Dupuis, L. Amyotrophic lateral sclerosis: all roads lead to Rome. J. Neurochem., 2007, 101, 1153-1160.
7. Hasegawa, M.; Arai, T.; Nonaka, T.; Kametani, F.; Yoshida, M.; Hashizume, Y.; Beach, T. G.; Buratti, E.; Baralle, F.; Morita, M.; Nakano, I.; Oda, T.; Tsuchiya, K.; Akiyama, H. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann. Neurol., 2008, 64, 60-70.
8. Trapp, B. D.; Stys, P. K. Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol., 2009, 8, 280-291.
9. Turner, M. R.; Hardiman, O.; Benatar, M.; Brooks, B. R.; Chio, A.; De Carvalho, M.; Ince, P. G.; Lin, C.; Miller, R. G.; Mitsumoto, H.; Nicholson, G.; Ravits, J.; Shaw, P. J.; Swash, M.; Talbot, K.; Traynor, B. J.; Van Den Berg, L. H.; Veldink, J. H.; Vucic, S.; Kiernan, M. C. Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol., 2013, 12, 310-322.
10. Smith, R. A.; Miller, T. M.; Yamanaka, K.; Monia, B. P.; Condon, T. P.; Hung, G.; Lobsiger, C. S.; Ward, C. M.; McAlonis-Downes, M.; Wei, H.; Wancewicz, E. V.; Bennett, C. F.; Cleveland, D. W. Antisense oligonucleotide therapy for neurodegenerative disease. J. Clin. Invest., 2006, 116, 2290-2296.
11. Marc, G.; Leah, R.; Ofira, E.; Oded, A.; Zohar, A.; Hanna, R. Presymptomatic treatment with acetylcholinesterase antisense oligonucleotides prolongs survival in ALS (G93A-SOD1) mice. Biomed. Res. Int., 2013, 2013, 845345.
12. Donnelly Christopher, J.; Zhang, P.-W.; Pham Jacqueline, T.; Haeusler Aaron, R.; Mistry Nipun, A.; Vidensky, S.; Daley Elizabeth, L.; Poth Erin, M.; Hoover, B.; Fines Daniel, M.; Maragakis, N.; Tienari Pentti, J.; Petrucelli, L.; Traynor Bryan, J.; Wang, J.; Rigo, F.; Bennett, C. F.; Blackshaw, S.; Sattler, R.; Rothstein Jeffrey, D. RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention. Neuron, 2013, 80, 415-428.
13. Miller, T. M.; Pestronk, A.; David, W.; Rothstein, J.; Simpson, E.; Appel, S. H.; Andres, P. L.; Mahoney, K.; Allred, P.; Alexander, K.; Ostrow, L. W.; Schoenfeld, D.; Macklin, E. A.; Norris, D. A.; Manousakis, G.; Crisp, M.; Smith, R.; Bennett, C. F.; Bishop, K. M.; Cudkowicz, M. E. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol., 2013, 12, 435-442.
14. Watkins, J. C.; Evans, R. H. Excitatory amino acid transmitters. Annu. Rev. Pharmacol. Toxicol., 1981, 21, 165-204.
15. Heath, P. R.; Shaw, P. J. Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle Nerve, 2002, 26, 438-458.
16. Dong, H.; Zhang, P.; Song, I.; Petralia, R. S.; Liao, D.; Huganir, R. L. Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2. J. Neurosci., 1999, 19, 6930-6941.
17. Vandenberg, R. J. Molecular pharmacology and physiology of glutamate transporters in the central nervous system. Clin. Exp. Pharmacol. Physiol., 1998, 25, 393-400.
18. Laake, J. H.; Slyngstad, T. A.; Haug, F. M.; Ottersen, O. P. Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: immunogold evidence from hippocampal slice cultures. J. Neurochem., 1995, 65, 871-881.
19. Simeone, T. A.; Sanchez, R. M.; Rho, J. M. Molecular biology and ontogeny of glutamate receptors in the mammalian central nervous system. J. Child Neurol., 2004, 19, 343-360.
20. MacDermott, A. B.; Mayer, M. L.; Westbrook, G. L.; Smith, S. J.; Barker, J. L. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature, 1986, 321, 519-522.
21. Traven, H. G.; Brodin, L.; Lansner, A.; Ekeberg, O.; Wallen, P.; Grillner, S. Computer simulations of NMDA and non-NMDA receptor-mediated synaptic drive: sensory and supraspinal modulation of neurons and small networks. J. Neurophysiol., 1993, 70, 695-709.
22. Komuro, H.; Rakic, P. Modulation of neuronal migration by NMDA receptors. Science, 1993, 260, 95-97.
23. Bliss, T. V.; Collingridge, G. L. A synaptic model of memory: longterm potentiation in the hippocampus. Nature, 1993, 361, 31-39.
24. Kutsuwada, T.; Kashiwabuchi, N.; Mori, H.; Sakimura, K.; Kushiya, E.; Araki, K.; Meguro, H.; Masaki, H.; Kumanishi, T.; Arakawa, M.; et al. Molecular diversity of the NMDA receptor channel. Nature, 1992, 358, 36-41.
25. Meguro, H.; Mori, H.; Araki, K.; Kushiya, E.; Kutsuwada, T.; Yamazaki, M.; Kumanishi, T.; Arakawa, M.; Sakimura, K.; Mishina, M. Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature, 1992, 357, 70-74.
26. Michaelis, E. K. Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog. Neurobiol., 1998, 54, 369-415.
27. Monyer, H.; Sprengel, R.; Schoepfer, R.; Herb, A.; Higuchi, M.; Lomeli, H.; Burnashev, N.; Sakmann, B.; Seeburg, P. H. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science, 1992, 256, 1217-1221.
28. Ishii, T.; Moriyoshi, K.; Sugihara, H.; Sakurada, K.; Kadotani, H.; Yokoi, M.; Akazawa, C.; Shigemoto, R.; Mizuno, N.; Masu, M.; et al. Molecular characterization of the family of the N-methyl-Daspartate receptor subunits. J. Biol. Chem., 1993, 268, 2836-2843.
29. Watanabe, M.; Inoue, Y.; Sakimura, K.; Mishina, M. Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the brain. Ann. N. Y. Acad. Sci., 1993, 707, 463-466.
30. Watanabe, M.; Inoue, Y.; Sakimura, K.; Mishina, M. Distinct distributions of five N-methyl-D-aspartate receptor channel subunit mRNAs in the forebrain. J. Comp. Neurol., 1993, 338, 377-390.
31. Watanabe, M.; Mishina, M.; Inoue, Y. Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem. J. Comp. Neurol., 1994, 343, 520-531.
32. Watanabe, M.; Mishina, M.; Inoue, Y. Distinct spatiotemporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum. J. Comp. Neurol., 1994, 343, 513-519.
33. Ciabarra, A. M.; Sevarino, K. A. An anti-chi-1 antibody recognizes a heavily glycosylated protein in rat brain. Brain Res. Mol. Brain Res., 1997, 46, 85-90.
34. Nishi, M.; Hinds, H.; Lu, H. P.; Kawata, M.; Hayashi, Y. Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner. J. Neurosci., 2001, 21, RC185.
35. Chatterton, J. E.; Awobuluyi, M.; Premkumar, L. S.; Takahashi, H.; Talantova, M.; Shin, Y.; Cui, J.; Tu, S.; Sevarino, K. A.; Nakanishi, N.; Tong, G.; Lipton, S. A.; Zhang, D. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature, 2002, 415, 793-798.
36. Dingledine, R.; Borges, K.; Bowie, D.; Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev., 1999, 51, 7-61.
37. Rothstein, J.; Martin, L.; Kuncl, R. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N. Engl. J. Med., 1992, 326, 1464-1468.
38. Rothstein, J.; Van Kammen, M.; Levey, A.; Martin, L.; Kuncl, R. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol., 1995, 38, 73-84.
39. Boillee, S.; Vande Velde, C.; Cleveland, D. W. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron, 2006, 52, 39-59.
40. 2+) overload of motor neurons. Amyotroph. Lateral. Scler., 2007, 8, 260-265.
41. Rothstein, J. D.; Jin, L.; Dykes-Hoberg, M.; Kuncl, R. W. Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity. Proc. Natl. Acad. Sci. USA, 1993, 90, 6591-6595.
42. Rothstein, J. D.; Van Kammen, M.; Levey, A. I.; Martin, L. J.; Kuncl, R. W. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol., 1995, 38, 73-84.
43. Trotti, D.; Rolfs, A.; Danbolt, N. C.; Brown, R. H. Jr.; Hediger, M. A. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nat. Neurosci., 1999, 2, 848.
44. Boston-Howes, W.; Gibb, S. L.; Williams, E. O.; Pasinelli, P.; Brown, R. H. Jr.; Trotti, D. Caspase-3 cleaves and inactivates the glutamate transporter EAAT2. J. Biol. Chem., 2006, 281, 14076-14084.
45. Gibb, S. L.; Boston-Howes, W.; Lavina, Z. S.; Gustincich, S.; Brown, R. H. Jr.; Pasinelli, P.; Trotti, D. A Caspase-3-cleaved Fragment of the Glial Glutamate Transporter EAAT2 Is Sumoylated and Targeted to Promyelocytic Leukemia Nuclear Bodies in Mutant SOD1-linked Amyotrophic Lateral Sclerosis. J. Biol. Chem., 2007, 282, 32480-32490.
46. Rothstein, J. D.; Patel, S.; Regan, M. R.; Haenggeli, C.; Huang, Y. H.; Bergles, D. E.; Jin, L.; Dykes Hoberg, M.; Vidensky, S.; Chung, D. S.; Toan, S. V.; Bruijn, L. I.; Su, Z. Z.; Gupta, P.; Fisher, P. B. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature, 2005, 433, 73-77.
47. Guo, H.; Lai, L.; Butchbach, M. E.; Stockinger, M. P.; Shan, X.; Bishop, G. A.; Lin, C. L. Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice. Hum. Mol. Genet., 2003, 12, 2519-2532.
48. Kawahara, Y.; Ito, K.; Sun, H.; Aizawa, H.; Kanazawa, I.; Kwak, S. Glutamate receptors: RNA editing and death of motor neurons. Nature, 2004, 427, 801.
49. Kwak, S.; Kawahara, Y. Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis. J. Mol. Med., 2005, 83, 110-120.
50. Van Damme, P.; Braeken, D.; Callewaert, G.; Robberecht, W.; Van Den Bosch, L. GluR2 deficiency accelerates motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol., 2005, 64, 605-612.
51. Van Damme, P.; Van Den Bosch, L.; Van Houtte, E.; Callewaert, G.; Robberecht, W. GluR2-dependent properties of AMPA receptors determine the selective vulnerability of motor neurons to excitotoxicity. J. Neurophysiol., 2002, 88, 1279-1287.
52. Ince, P.; Stout, N.; Shaw, P.; Slade, J.; Hunziker, W.; Heizmann, C. W.; Baimbridge, K. G. Parvalbumin and calbindin D-28k in the human motor system and in motor neuron disease. Neuropathol. Appl. Neurobiol., 1993, 19, 291-299.
53. 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.
54. Choe, C. U.; Ehrlich, B. E. The inositol 1, 4, 5-trisphosphate receptor (IP3R) and its regulators: sometimes good and sometimes bad teamwork. Sci. STKE, 2006, 2006, re15.
55. Gutstein, D. E.; Marks, A. R. Role of inositol 1, 4, 5-trisphosphate receptors in regulating apoptotic signaling and heart failure. Heart Vessels, 1997, Suppl. 12, 53-57.
56. Amendola, J.; Durand, J. Morphological differences between wildtype and transgenic superoxide dismutase 1 lumbar motoneurons in postnatal mice. J. Comp. Neurol., 2008, 511, 329-341.
57. Quinlan, K. A. Links between Electrophysiological and Molecular Pathology of Amyotrophic Lateral Sclerosis. Integ. Comp. Biol., 2011, 51, 913-925.
58. Choi, D. W. Ionic dependence of glutamate neurotoxicity. J. Neurosci., 1987, 7, 369-379.
59. Shaw, P.; Kuncl, R. Current concepts in the pathogenesis of ALS. In: WR K, ed. Motor Neuron Disease. Lodon: WB Saunders; 2002, 37-73.
60. Stys, P. K. Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. J. Cereb. Blood Flow Metab., 1998, 18, 2-25.
61. 2+ channels and their regulation by excitatory amino acids. Ann. N. Y. Acad. Sci., 1989, 568, 149-158.
62. Meldrum, B.; Garthwaite, J. Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol. Sci., 1990, 11, 379-387.
63. Regan, R. F.; Panter, S. S.; Witz, A.; Tilly, J. L.; Giffard, R. G. Ultrastructure of excitotoxic neuronal death in murine cortical culture. Brain Res., 1995, 705, 188-198.
64. Cox, L.; Kirby, J.; Shaw, P. Pathogenesis of motor neurone disease. In: Kiernan M, ed. The Motor Neurone Disease Handbook. Sydney: Australasian Medical Publishing Company Limited; 2007, 26-55.
65. Bondy, S. C.; Lee, D. K. Oxidative stress induced by glutamate receptor agonists. Brain Res., 1993, 610, 229-233.
66. Lees, G. J. Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience, 1993, 54, 287-322.
67. Maher, P.; Davis, J. B. The role of monoamine metabolism in oxidative glutamate toxicity. J. Neurosci., 1996, 16, 6394-6401.
68. Bensimon, G.; Lacomblez, L.; Meininger, V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N. Engl. J. Med., 1994, 330, 585-591.
69. Gurney, M. E.; Cutting, F. B.; Zhai, P.; Doble, A.; Taylor, C. P.; Andrus, P. K.; Hall, E. D. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann. Neurol., 1996, 39, 147-157.
70. Gurney, M. E.; Fleck, T. J.; Himes, C. S.; Hall, E. D. Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology, 1998, 50, 62-66.
71. Lacomblez, L.; Bensimon, G.; Leigh, P. N.; Guillet, P.; Meininger, V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet, 1996, 347, 1425-1431.
72. Wang, S. J.; Wang, K. Y.; Wang, W. C. Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Neuroscience, 2004, 125, 191-201.
73. Azbill, R. D.; Mu, X.; Springer, J. E. Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res., 2000, 871, 175-180.
74. Cheah, B. C.; Vucic, S.; Krishnan, A. V.; Kiernan, M. C. Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr. Med. Chem., 2010, 17, 1942-1199.
75. Bensimon, G.; Lacomblez, L.; Delumeau, J. C.; Bejuit, R.; Truffinet, P.; Meininger, V. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. J. Neurol., 2002, 249, 609-615.
76. Traynorm, B. J.; Alexander, M.; Corr, B.; Frost, E.; Hardiman, O. Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. J. Neurol. Neurosurg. Psychiatry, 2003, 74, 1258-1261.
77. Vucic, S.; Ziemann, U.; Eisen, A.; Hallett, M.; Kiernan, M. C. Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights. J. Neurol. Neurosurg. Psychiatry, 2013, 84, 1161-1170.
78. Eisen, A.; Kim, S.; Pant, B. Amyotrophic lateral sclerosis (ALS): a phylogenetic disease of the corticomotoneuron? Muscle Nerve, 1992, 15, 219-224.
79. Vucic, S.; Kiernan, M. Pathophysiology of degeneration in familial amyotrophic lateral sclerosis. Curr. Mol. Med., 2009, 9, 255-272.
80. Lemon, R. N.; Griffiths, J. Comparing the function of the corticospinal system in different species: organizational differences for motor specialization? Muscle Nerve, 2005, 32, 261-279.
81. Armand, J. The origin, course and terminations of corticospinal fibers in various mammals. Prog. Brain Res., 1982, 57, 329-360.
82. Eisen, A. A.; Shtybel, W. AAEM minimonograph #35: Clinical experience with transcranial magnetic stimulation. Muscle Nerve, 1990, 13, 995-1011.
83. Wilbourn, A. J. The "split hand syndrome". Muscle Nerve, 2000, 23, 138.
84. Kuwabara, S.; Sonoo, M.; Komori, T.; Shimizu, T.; Hirashima, F.; Inaba, A.; Misawa, S.; Hatanaka, Y. Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity. Muscle Nerve, 2008, 37, 426-430.
85. Eisen, A.; Kuwabara, S. The split hand syndrome in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry, 2012, 83, 399-403.
86. Menon, P.; Bae, J. S.; Mioshi, E.; Kiernan, M. C.; Vucic, S. Splithand plus sign in ALS: Differential involvement of the flexor pollicis longus and intrinsic hand muscles. Amyotroph. Lateral Scler. Frontotemporal Degener., 2013, 14(4), 315-318.
87. Menon, P.; Kiernan, M. C.; Vucic, S. Appearance, phenomenology and diagnostic utility of the split hand in amyotrophic lateral sclerosis. Neurodeg. Dis. Manag., 2011, 1, 457-462.
88. Caramia, M. D.; Cicinelli, P.; Paradiso, C.; Mariorenzi, R.; Zarola, F.; Bernardi, G.; Rossini, P. M. Excitability changes of muscular responses to magnetic brain stimulation in patients with central motor disorders. Electroencephalogr. Clin. Neurophysiol., 1991, 81, 243-250.
89. Desiato, M.; Bernardi, G.; Hagi, A. H.; Boffa, L.; Caramia, M. D. Transcranial magnetic stimulation of motor pathways directed to muscles supplied by cranial nerves in ALS. Clin. Neurophysiol., 2002, 113, 132-140.
90. Eisen, A.; Pant, B.; Stewart, H. Cortical excitability in amyotrophic lateral sclerosis: a clue to pathogenesis. Can. J. Neurol. Sci., 1993, 20, 11-16.
91. Prout, A. J.; Eisen, A. The cortical silent period and ALS. Muscle Nerve, 1994, 17, 217-223.
92. Vucic, S.; Kiernan, M. C. Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease. Brain, 2006, 129, 2436-2446.
93. Vucic, S.; Kiernan, M. C. Upregulation of persistent sodium conductances in familial ALS. J. Neurol. Neurosurg. Psychiatry, 2010, 81, 222-227.
94. Vucic, S.; Nicholson, G. A.; Kiernan, M. C. Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain, 2008, 131, 1540-1550.
95. 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, 2010, 81, 1286-1288.
96. Williams, K. L.; Fifita, J. A.; Vucic, S.; Durnall, J. C.; Kiernan, M. C.; Blair, I. P.; Nicholson, G. A. Pathophysiological insights into ALS with C9ORF72 expansions. J. Neurol. Neurosurg. Psychiatry, 2013, 84(8), 931-935.
97. Zanette, G.; Tamburin, S.; Manganotti, P.; Refatti, N.; Forgione, A.; Rizzuto, N. Different mechanisms contribute to motor cortex hyperexcitability in amyotrophic lateral sclerosis. Clin. Neurophysiol., 2002, 113, 1688-1697.
98. Saxena, S.; Roselli, F.; Singh, K.; Leptien, K.; Julien, J.-P.; Gros-Louis, F.; Caroni, P. Neuroprotection through Excitability and mTOR Required in ALS Motoneurons to Delay Disease and Extend Survival. Neuron, 2013, 80, 80-96.
99. La Spada, A. R.; Wilson, E. M.; Lubahn, D. B.; Harding, A. E.; Fischbeck, K. H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature, 1991, 352, 77-79.
100. Kennedy, W. R.; Alter, M.; Sung, J. H. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology, 1968, 18, 671-680.
101. Vucic, S.; Kiernan, M. C. Abnormalities in cortical and peripheral excitability in flail arm variant amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry, 2007, 78, 849-852.
102. Vucic, S.; Cheah, B. C.; Yiannikas, C.; Kiernan, M. C. Cortical excitability distinguishes ALS from mimic disorders. Clin. Neurophysiol., 2011, 122, 1860-1866.
103. Vucic, S.; Cheah, B. C.; Yiannikas, C.; Vincent, A.; Kiernan, M. C. Corticomotoneuronal function and hyperexcitability in acquired neuromyotonia. Brain, 2010, 133, 2727-2733.
104. Vucic, S.; Nicholson, G. A.; Kiernan, M. C. Cortical excitability in hereditary motor neuronopathy with pyramidal signs: comparison with ALS. J. Neurol. Neurosurg. Psychiatry, 2010, 81, 97-100.
105. Vucic, S.; Stein, T. D.; Hedley-Whyte, E. T.; Reddel, S. R.; Tisch, S.; Kotschet, K.; Cros, D.; Kiernan, M. C. FOSMN syndrome: novel insight into disease pathophysiology. Neurology, 2012, 79, 73-79.
106. Browne, S. E.; Yang, L.; DiMauro, J. P.; Fuller, S. W.; Licata, S. C.; Beal, M. F. Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS. Neurobiol. Dis., 2006, 22, 599-610.
107. Lillo, P.; Hodges, J. R. Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J. Clin. Neurosci., 2009, 16, 1131-1135.
108. 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.-Y. Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis. Science, 2006, 314, 130-133.
109. Renton Alan, E.; Majounie, E.; Waite, A.; Simón-Sánchez, J.; Rollinson, S.; Gibbs, J. R.; Schymick Jennifer, C.; Laaksovirta, H.; Van Swieten John, C.; Myllykangas, L.; Kalimo, H.; Paetau, A.; Abramzon, Y.; Remes Anne, M.; Kaganovich, A.; Scholz Sonja, W.; Duckworth, J.; Ding, J.; Harmer Daniel, W.; Hernandez Dena, G.; Johnson Janel, O.; Mok, K.; Ryten, M.; Trabzuni, D.; Guerreiro Rita, J.; Orrell Richard, W.; Neal, J.; Murray, A.; Pearson, J.; Jansen Iris, E.; Sondervan, D.; Seelaar, H.; Blake, D.; Young, K.; Halliwell, N.; Callister Janis, B.; Toulson, G.; Richardson, A.; Gerhard, A.; Snowden, J.; Mann, D.; Neary, D.; Nalls Michael, A.; Peuralinna, T.; Jansson, L.; Isoviita, V.-M.; Kaivorinne, A.-L.; Hölttä-Vuori, M.; Ikonen, E.; Sulkava, R.; Benatar, M.; Wuu, J.; Chiò, A.; Restagno, G.; Borghero, G.; Sabatelli, M.; Heckerman, D.; Rogaeva, E.; Zinman, L.; Rothstein Jeffrey, D.; Sendtner, M.; Drepper, C.; Eichler Evan, E.; Alkan, C.; Abdullaev, Z.; Pack Svetlana, D.; Dutra, A.; Pak, E.; Hardy, J.; Singleton, A.; Williams Nigel, M.; Heutink, P.; Pickering-Brown, S.; Morris Huw, R.; Tienari Pentti, J.; Traynor Bryan, J. A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD. Neuron, 2011, 72, 257-268.
110. DeJesus-Hernandez, M.; Mackenzie Ian, R.; Boeve Bradley, F.; Boxer Adam, L.; Baker, M.; Rutherford Nicola, J.; Nicholson Alexandra, M.; Finch NiCole, A.; Flynn, H.; Adamson, J.; Kouri, N.; Wojtas, A.; Sengdy, P.; Hsiung G. Yuek, R.; Karydas, A.; Seeley William, W.; Josephs Keith, A.; Coppola, G.; Geschwind Daniel, H.; Wszolek Zbigniew, K.; Feldman, H.; Knopman David, S.; Petersen Ronald, C.; Miller Bruce, L.; Dickson Dennis, W.; Boylan Kevin, B.; Graff-Radford Neill, R.; Rademakers, R. Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS. Neuron, 2011, 72, 245-256.
111. Traynor, B. J. Road to the chromosome 9p-linked ALS/FTD locus. J. Neurol. Neurosurg. Psychiatry, 2012, 83, 356-357.
112. Boillee, S.; Yamanaka, K.; Lobsiger, C. S.; Copeland, N. G.; Jenkins, N. A.; Kassiotis, G.; Kollias, G.; Cleveland, D. W. Onset and progression in inherited ALS determined by motor neurons and microglia. Science, 2006, 312, 1389-1392.
113. Nagai, M. Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. J. Neurosci., 2001, 21, 9246-9254.
114. Haidet-Phillips, A. M.; Hester, M. E.; Miranda, C. J.; Meyer, K.; Braun, L.; Frakes, A.; Song, S.; Likhite, S.; Murtha, M. J.; Foust, K. D.; Rao, M.; Eagle, A.; Kammesheidt, A.; Christensen, A.; Mendell, J. R.; Burghes, A. H. M.; Kaspar, B. K. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat. Biotech., 2011, 29, 824-828.
115. Yamanaka, K.; Chun, S. J.; Boillee, S.; Fujimori-Tonou, N.; Yamashita, H.; Gutmann, D. H.; Takahashi, R.; Misawa, H.; Cleveland, D. W. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci., 2008, 11, 251-253.
116. Lino, M. M.; Schneider, C.; Caroni, P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J. Neurosci., 2002, 22, 4825-4832.
117. Pramatarova, A.; Laganiere, J.; Roussel, J.; Brisebois, K.; Rouleau, G. A. Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J. Neurosci., 2001, 21, 3369-3374.
118. Gong, Y. H.; Parsadanian, A. S.; Andreeva, A.; Snider, W. D.; Elliott, J. L. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J. Neurosci., 2000, 20, 660-665.
119. Gordon, P.; Corcia, P.; Meininger, V. New therapy options for amyotrophic lateral sclerosis. Expert Opin. Pharmacother., 2013, 14, 1907-1917.
120. Corti, S.; Locatelli, F.; Papadimitriou, D.; Del Bo, R.; Nizzardo, M.; Nardini, M.; Donadoni, C.; Salani, S.; Fortunato, F.; Strazzer, S.; Bresolin, N.; Comi, G. P. Neural stem cells LewisX + CXCR4 + modify disease progression in an amyotrophic lateral sclerosis model. Brain, 2007, 130, 1289-1305.
121. Xu, L.; Ryugo, D. K.; Pongstaporn, T.; Johe, K.; Koliatsos, V. E. Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: Differentiation and structural integration into the segmental motor circuitry. J. Comp. Neurol., 2009, 514, 297-309.
122. Teng, Y. D.; Benn, S. C.; Kalkanis, S. N.; Shefner, J. M.; Onario, R. C.; Cheng, B.; Lachyankar, M. B.; Marconi, M.; Li, J.; Yu, D.; Han, I.; Maragakis, N. J.; Lládo, J.; Erkmen, K.; Redmond, D. E.; Sidman, R. L.; Przedborski, S.; Rothstein, J. D.; Brown, R. H.; Snyder, E. Y. Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis. Sci. Transl. Med., 2012, 4, 165ra4.
123. Hefferan, M. P.; Galik, J.; Kakinohana, O.; Sekerkova, G.; Santucci, C.; Marsala, S.; Navarro, R.; Hruska-Plochan, M.; Johe, K.; Feldman, E.; Cleveland, D. W.; Marsala, M. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation. PLoS One, 2012, 7, e42614.
124. Glass, J. D.; Boulis, N. M.; Johe, K.; Rutkove, S. B.; Federici, T.; Polak, M.; Kelly, C.; Feldman, E. L. Lumbar Intraspinal Injection of Neural Stem Cells in Patients with Amyotrophic Lateral Sclerosis: Results of a Phase I Trial in 12 Patients. Stem Cells, 2012, 30, 1144-1151.
125. Boucherie, C.; Schäfer, S.; Lavand'homme, P.; Maloteaux, J.-M.; Hermans, E. Chimerization of astroglial population in the lumbar spinal cord after mesenchymal stem cell transplantation prolongs survival in a rat model of amyotrophic lateral sclerosis. J. Neurosci. Res., 2009, 87, 2034-2046.
126. Mazzini, L.; Ferrero, I.; Luparello, V.; Rustichelli, D.; Gunetti, M.; Mareschi, K.; Testa, L.; Stecco, A.; Tarletti, R.; Miglioretti, M.; Fava, E.; Nasuelli, N.; Cisari, C.; Massara, M.; Vercelli, R.; Oggioni, G. D.; Carriero, A.; Cantello, R.; Monaco, F.; Fagioli, F. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp. Neurol., 2010, 223, 229-237.
127. Karussis, D.; Karageorgiou, C.; Vaknin-Dembinsky, A.; Gowda-Kurkalli, B.; Gomori, J. M.; Kassis, I.; Bulte, J. W.; Petrou, P.; Ben-Hur, T.; Abramsky, O.; Slavin, S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch. Neurol., 2010, 67, 1187-1194.
128. Mitne-Neto, M.; Machado-Costa, M.; Marchetto, M. C. N.; Bengtson, M. H.; Joazeiro, C. A.; Tsuda, H.; Bellen, H. J.; Silva, H. C. A.; Oliveira, A. S. B.; Lazar, M.; Muotri, A. R.; Zatz, M. Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients. Hum. Mol. Genet., 2011, 20, 3642-3652.
129. Burkhardt, M. F.; Martinez, F. J.; Wright, S.; Ramos, C.; Volfson, D.; Mason, M.; Garnes, J.; Dang, V.; Lievers, J.; Shoukat-Mumtaz, U.; Martinez, R.; Gai, H.; Blake, R.; Vaisberg, E.; Grskovic, M.; Johnson, C.; Irion, S.; Bright, J.; Cooper, B.; Nguyen, L.; Griswold-Prenner, I.; Javaherian, A. A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells. Mol. Cell. Neurosci., 2013, 56, 355-364.
130. Kiernan, M. C. Hyperexcitability, persistent Na+ conductances and neurodegeneration in amyotrophic lateral sclerosis. Exp. Neurol., 2009, 218, 1-4.
131. French, C. R.; Sah, P.; Buckett, K. J.; Gage, P. W. A voltagedependent persistent sodium current in mammalian hippocampal neurons. J. Gen. Physiol., 1990, 95, 1139-1157.
132. Crill, W. E. Persistent sodium current in mammalian central neurons. Annu Rev. Physiol., 1996, 58, 349-362.
133. Bostock, H.; Rothwell, J. C. Latent addition in motor and sensory fibres of human peripheral nerve. J. Physiol. (Lond.), 1997, 498, 277-294.
134. Catterall, W. A.; Goldin, A. L.; Waxman, S. G. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol. Rev., 2005, 57, 397-409.
135. Baker, M. D.; Bostock, H. Inactivation of macroscopic late Na+ current and characteristics of unitary late Na+ currents in sensory neurons. J. Neurophysiol., 1998, 80, 2538-2549.
136. Catterall, W. A. Voltage-gated sodium channels at 60: structure, function and pathophysiology. J. Physiol., 2012, 590, 2577-2589.
137. Goldin, A. L. Resurgence of sodium channel research. Annu. Rev. Physiol., 2001, 63, 871-894.
138. Kuo, J. J.; Siddique, T.; Fu, R.; Heckman, C. J. Increased persistent Na (+) current and its effect on excitability in motoneurones cultured from mutant SOD1 mice. J. Physiol. (Lond), 2005, 563, 843-854.
139. Pieri, M.; Carunchio, I.; Curcio, L.; Mercuri, N. B.; Zona, C. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis. Exp. Neurol., 2009, 215, 368-379.
140. Urbani, A.; Belluzzi, O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur. J. Neurosci., 2000, 12, 3567-3574.
141. Vucic, S.; Lin, C. S.-Y.; Cheah, B. C.; Murray, J.; Menon, P.; Krishnan, A. V.; Kiernan, M. C. Riluzole exerts central and peripheral modulating effects in amyotrophic lateral sclerosis. Brain, 2013, 136, 1361-1370.
142. Bostock, H. The strength-duration relationship for excitation of myelinated nerve: computed dependence on membrane parameters. J. Physiol. (Lond), 1983, 341, 59-74.
143. Mogyoros, I.; Lin, C.; Dowla, S.; Grosskreutz, J.; Burke, D. Strength-duration properties and their voltage dependence at different sites along the median nerve. Clin. Neurophysiol., 1999, 110, 1618-1624.
144. Mogyoros, I.; Kiernan, M. C.; Burke, D. Strength-duration properties of human peripheral nerve. Brain, 1996, 119, 439-447.
145. Weiss, G. Sur la possibilité de rendre comparables entre eux les appareils servant l'excitation électrique. Arch. Ital. Biol., 1901, 35, 413-446.
146. Mogyoros, I.; Kiernan, M.; Burke, D.; Bostock, H. Strengthduration properties of sensory and motor axons in amyotrophic lateral sclerosis. Brain, 1998, 121, 851-859.
147. Kanai, K.; Kuwabara, S.; Misawa, S.; Tamura, N.; Ogawara, K.; Nakata, M.; Sawai, S.; Hattori, T.; Bostock, H. Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage. Brain, 2006, 129, 953-962.
148. Vucic, S.; Kiernan, M. C. Axonal excitability properties in amyotrophic lateral sclerosis. Clin. Neurophysiol., 2006, 117, 1458-1466.
149. Tamura, N.; Kuwabara, S.; Misawa, S.; Kanai, K.; Nakata, M.; Sawai, S.; Hattori, T. Increased nodal persistent Na+ currents in human neuropathy and motor neuron disease estimated by latent addition. Clin. Neurophysiol., 2006, 117, 2451-2458.
150. Menon, P.; Kiernanm M, C.; Vucicm S. ALS pathophysiology: Insights form the split-hand phenomenon. Clin. Neurophysiol., 2014, 125(1), 186-193.
151. Shibuya, K.; Misawa, S.; Nasu, S.; Sekiguchi, Y.; Mitsuma, S.; Beppu, M.; Ohmori, S.; Iwai, Y.; Ito, S.; Kanai, K.; Sato, Y.; Kuwabara, S. Split hand syndrome in amyotrophic lateral sclerosis: different excitability changes in the thenar and hypothenar motor axons. J. Neurol. Neurosurg. Psychiatry, 2013, 84, 969-972.
152. Kanai, K.; Kuwabara, S.; Arai, K.; Sung, J. Y.; Ogawara, K.; Hattori, T. Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment. Brain, 2003, 126, 965-973.
153. 2+ influx during anoxia in mammalian central nervous system white matter. Ann. Neurol., 1991, 30, 375-380.
154. 2+ influx during anoxia in mammalian CNS white matter. Ann. N. Y. Acad. Sci., 1991, 639, 328-332.
155. Carafoli, E.; Santella, L.; Branca, D.; Brini, M. Generation, Control, and Processing of Cellular Calcium Signals. Crit. Rev. in Biochem. and Mol. Biol., 2001, 36, 107-260.
156. 2+)-mediated injury in CNS white matter. Trends Neurosci., 1991, 14, 461-468.
157. Ellis, D. Z.; Rabe, J.; Sweadner, K. J. Global loss of Na, K-ATPase and its nitric oxide-mediated regulation in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurosci., 2003, 23, 43-51.
158. Vucic, S.; Krishnan, A. V.; Kiernan, M. C. Fatigue and activity dependent changes in axonal excitability in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry, 2007, 78, 1202-1208.
159. Stys, P. K. Sodium channel blockers as neuroprotectants in neuroinflammatory disease: a double-edged sword. Ann. Neurol., 2007, 62, 3-5.
160. 2+ exchanger. J. Neurosci., 1992, 12, 430-439.
161. Bechtold, D. A.; Kapoor, R.; Smith, K. J. Axonal protection using flecainide in experimental autoimmune encephalomyelitis. Ann. Neurol., 2004, 55, 607-616.
162. Bechtold, D. A.; Smith, K. J. Sodium-mediated axonal degeneration in inflammatory demyelinating disease. J. Neurol. Sci., 2005, 233, 27-35.
163. Lo, A. C.; Saab, C. Y.; Black, J. A.; Waxman, S. G. Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. J. Neurophysiol., 2003, 90, 3566-3571.
164. Black, J. A.; Liu, S.; Hains, B. C.; Saab, C. Y.; Waxman, S. G. Longterm protection of central axons with phenytoin in monophasic and chronic-relapsing EAE. Brain, 2006, 129, 3196-3208.
165. Black, J. A.; Waxman, S. G. Phenytoin protects central axons in experimental autoimmune encephalomyelitis. J. Neurol. Sci., 2008, 274, 57-63.
166. Bechtold, D.; Miller, S.; Dawson, A.; Sun, Y.; Kapoor, R.; Berry, D.; Smith, K. Axonal protection achieved in a model of multiple sclerosis using lamotrigine. J. Neurol., 2006, 253, 1542-1551.
167. Hewitt, K. E.; Stys, P. K.; Lesiuk, H. J. The use-dependent sodium channel blocker mexiletine is neuroprotective against global ischemic injury. Brain Res., 2001, 898, 281-287.
168. Chung, M. J.; Suh, Y. L. Ultrastructural changes of mitochondria in the skeletal muscle of patients with amyotrophic lateral sclerosis. Ultrastruct. Pathol., 2002, 26, 3-7.
169. Higgins, C. M.; Jung, C.; Xu, Z. ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci., 2003, 4, 16.
170. Kirkinezos, I. G.; Bacman, S. R.; Hernandez, D.; Oca-Cossio, J.; Arias, L. J.; Perez-Pinzon, M. A.; Bradley, W. G.; Moraes, C. T. Cytochrome c association with the inner mitochondrial membrane is impaired in the CNS of G93A-SOD1 mice. J. Neurosci., 2005, 25, 164-172.
171. Lederer, C. W.; Torrisi, A.; Pantelidou, M.; Santama, N.; Cavallaro, S. Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis. BMC Genomics, 2007, 8, 26.
172. Xu, Z.; Jung, C.; Higgins, C.; Levine, J.; Kong, J. Mitochondrial degeneration in amyotrophic lateral sclerosis. J. Bioenerg. Biomembr., 2004, 36, 395-399.
173. Boillee, S. Onset and progression in inherited ALS determined by motor neurons and microglia. Science, 2006, 312, 1389-1392.
174. Dugan, L. L.; Choi, D. W. Excitotoxicity, free radicals, and cell membrane changes. Ann. Neurol., 1994, 35, 17-21.
175. Bowling, A. C.; Beal, M. F. Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci., 1995, 56, 1151-1171.
176. Kong, J.; Xu, Z. Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J. Neurosci., 1998, 18, 3241-3250.
177. Comi, G. P.; Bordoni, A.; Salani, S.; Franceschina, L.; Sciacco, M.; Prelle, 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, 110-116.
178. Fujita, K.; Yamauchi, M.; Shibayama, K.; Ando, M.; Honda, M.; Nagata, Y. Decreased cytochrome c oxidase activity but unchanged superoxide dismutase and glutathione peroxidase activities in the spinal cords of patients with amyotrophic lateral sclerosis. J. Neurosci. Res., 1996, 45, 276-281.
179. Jung, C.; Higgins, C. M.; Xu, Z. Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. J. Neurochem., 2002, 83, 535-545.
180. Bilsland, L. G.; Nirmalananthan, N.; Yip, J.; Greensmith, L.; Duchen, M. R. Expression of mutant SOD1G93A in astrocytes induces functional deficits in motoneuron mitochondria. J. Neurochem., 2008, 107, 1271-1283.
181. 2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J. Neurochem., 2006, 96, 1349-1361.
182. Jaiswal, M.; Zech, W.-D.; Goos, M.; Leutbecher, C.; Ferri, A.; Zippelius, A.; Carri, M.; Nau, R.; Keller, B. Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease. BMC Neuroscience, 2009, 10, 64.
183. 2+ uptake is greater in mutant SOD1 than in wild-type mouse motor terminals. Proc. Nat. Acad. Sci. USA, 2009, 106, 2007-2011.
184. Li, Q.; Vande Velde, C.; Israelson, A.; Xie, J.; Bailey, A. O.; Dong, M.-Q.; Chun, S.-J.; Roy, T.; Winer, L.; Yates, J. R.; Capaldi, R. A.; Cleveland, D. W.; Miller, T. M. ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import. Proc. Nat. Acad. Sci. USA, 2010, 107, 21146-21151.
185. MacAskill, A. F.; Atkin, T. A.; Kittler, J. T. Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses. Eur. J. Neurosci., 2010, 32, 231-240.
186. MacAskill, A. F.; Rinholm, J. E.; Twelvetrees, A. E.; Arancibia-Carcamo, I. L.; Muir, J.; Fransson, A.; Aspenstrom, P.; Attwell, D.; Kittler, J. T. Miro1 Is a Calcium Sensor for Glutamate Receptor Current Medicinal Chemistry, 2014, Vol. 21, No. 31
187. Menon et al. Dependent Localization of Mitochondria at Synapses. Neuron., 2009, 61, 541-555.
188. Bilsland, L. G.; Sahai, E.; Kelly, G.; Golding, M.; Greensmith, L.; Schiavo, G. Deficits in axonal transport precede ALS symptoms in vivo. Proc. Natl. Acad. Sci. USA, 2010, 107, 20523-20528.
189. De Vos, K. J.; Chapman, A. L.; Tennant, M. E.; Manser, C.; Tudor, E. L.; Lau, K.-F.; Brownlees, J.; Ackerley, S.; Shaw, P. J.; McLoughlin, D. M.; Shaw, C. E.; Leigh, P. N.; Miller, C. C. J.; Grierson, A. J. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Human Molecular Genetics, 2007, 16, 2720-2728.
190. Cheah, B. C.; Kiernan, M. C. Dexpramipexole, the R (+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosis. IDrugs, 2010, 13, 911-920.
191. Cudkowicz, M.; Bozik, M. E.; Ingersoll, E. W.; Miller, R.; Mitsumoto, H.; Shefner, J.; Moore, D. H.; Schoenfeld, D.; Mather, J. L.; Archibald, D.; Sullivan, M.; Amburgey, C.; Moritz, J.; Gribkoff, V. K. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat. Med., 2011, 17, 1652-1656.
192. Cudkowicz, M. E.; Van Den Berg, L. H.; Shefner, J. M.; Mitsumoto, H.; Mora, J. S.; Ludolph, A.; Hardiman, O.; Bozik, M. E.; Ingersoll, E. W.; Archibald, D.; Meyers, A. L.; Dong, Y.; Farwell, W. R.; Kerr, D. A. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial. Lancet Neurol., 2013, 12, 1059-1067.
193. Majounie, E.; Renton, A. E.; Mok, K.; Dopper, E. G. P.; Waite, A.; Rollinson, S.; Chiò, A.; Restagno, G.; Nicolaou, N.; Simon-Sanchez, J.; Van Swieten, J. C.; Abramzon, Y.; Johnson, J. O.; Sendtner, M.; Pamphlett, R.; Orrell, R. W.; Mead, S.; Sidle, K. C.; Houlden, H.; Rohrer, J. D.; Morrison, K. E.; Pall, H.; Talbot, K.; Ansorge, O.; Hernandez, D. G.; Arepalli, S.; Sabatelli, M.; Mora, G.; Corbo, M.; Giannini, F.; Calvo, A.; Englund, E.; Borghero, G.; Floris, G. L.; Remes, A. M.; Laaksovirta, H.; McCluskey, L.; Trojanowski, J. Q.; Van Deerlin, V. M.; Schellenberg, G. D.; Nalls, M. A.; Drory, V. E.; Lu, C.-S.; Yeh, T.-H.; Ishiura, H.; Takahashi, Y.; Tsuji, S.; Le Ber, I.; Brice, A.; Drepper, C.; Williams, N.; Kirby, J.; Shaw, P.; Hardy, J.; Tienari, P. J.; Heutink, P.; Morris, H. R.; Pickering-Brown, S.; Traynor, B. J. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. The Lancet Neurology, 2012, 11, 323-330.
194. Al-Sarraj, S.; King, A.; Troakes, C.; Smith, B.; Maekawa, S.; Bodi, I.; Rogelj, B.; Al-Chalabi, A.; Hortobʇyi, T.; Shaw, C. E. P62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS. Act.a Neuropathologica, 2011, 122, 691-702.
195. Ling, S.-C.; Polymenidou, M.; Cleveland, Doní W. Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis. Neuron, 2013, 79, 416-438.
196. Zamiri, B.; Reddy, K.; Macgregor, R. B.; Pearson, C. E. TMPyP4 Distorts RNA G-Quadruplex Structures of the Disease-Associated r (GGGGCC) n Repeat of the C9orf72 Gene and Blocks Interaction of RNA-Binding Proteins. J. Biol. Chem., 2014, 289(8), 4653-4659.
197. Gijselinck, I.; Van Langenhove, T.; Van Der Zee, J.; Sleegers, K.; Philtjens, S.; Kleinberger, G.; Janssens, J.; Bettens, K.; Van Cauwenberghe, C.; Pereson, S.; Engelborghs, S.; Sieben, A.; De Jonghe, P.; Vandenberghe, R.; Santens, P.; De Bleecker, J.; Maes, G.; Bäumer, V.; Dillen, L.; Joris, G.; Cuijt, I.; Corsmit, E.; Elinck, E.; Van Dongen, J.; Vermeulen, S.; Van Den Broeck, M.; Vaerenberg, C.; Mattheijssens, M.; Peeters, K.; Robberecht, W.; Cras, P.; Martin, J.-J.; De Deyn, P. P.; Cruts, M.; Van Broeckhoven, C. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degenerationamyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol., 2012, 11, 54-65.
198. Ciura, S.; Lattante, S.; Le Ber, I.; Latouche, M.; Tostivint, H.; Brice, A.; Kabashi, E. Loss of function of C9orf72 causes motor deficits in a zebrafish model of Amyotrophic Lateral Sclerosis. Ann. Neurol., 2013, 74(2), 180-187.
199. Mori, K.; Lammich, S.; Mackenzie, I. R.; Forne, I.; Zilow, S.; Kretzschmar, H.; Edbauer, D.; Janssens, J.; Kleinberger, G.; Cruts, M.; Herms, J.; Neumann, M.; Van Broeckhoven, C.; Arzberger, T.; Haass, C. hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations. Acta. Neuropathol., 2013, 125, 413-423.
200. Biffi, G.; Tannahill, D.; McCafferty, J.; Balasubramanian, S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nat. Chem., 2013, 5, 182-186.
201. Miura, T.; Benevides, J. M.; Thomas, Jr. G. J. A phase diagram for sodium and potassium ion control of polymorphism in telomeric DNA. J. Mol. Biol., 1995, 248, 233-238.
202. Zu, T.; Gibbens, B.; Doty, N. S.; Gomes-Pereira, M.; Huguet, A.; Stone, M. D.; Margolis, J.; Peterson, M.; Markowski, T. W.; Ingram, M. A. C.; Nan, Z.; Forste, R C.; Low, W. C.; Schoser, B.; Somia, N. V.; Clark, H. B.; Schmechel, S.; Bitterman, P. B.; Gourdon, G.; Swanson, M. S.; Moseley, M.; Ranu, L. P. W. Non-ATG-initiated translation directed by microsatellite expansions. Proc. Natl. Acad. Sci. USA, 2011, 108, 260-265.
203. Mori, K.; Weng, S.-M.; Arzberger, T.; May, S.; Rentzsch, K.; Kremmer, E.; Schmid, B.; Kretzschmar, H. A.; Cruts, M.; Van Broeckhoven, C.; Haass, C.; Edbauer, D. The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS. Science, 2013, 339, 1335-1338.
204. Ash Peter, E. A.; Bieniek Kevin, F.; Gendron Tania, F.; Caulfield, T.; Lin, W.-L.; DeJesus-Hernandez, M.; Van Blitterswijk, Marka, M.; Jansen-West, K.; Paul, Joseph, W.; Rademakers, R.; Boylan Kevin, B.; Dickson Dennis, W.; Petrucelli, L. Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS. Neuron., 2013, 77, 639-646.
205. 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, 1668-1672.
206. 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-Saraj, 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, 1208-1211.
207. Andersen, P. M.; Al-Chalabi, A. Clinical genetics of amyotrophic lateral sclerosis: what do we really know?. Nat. Rev. Neurol., 2011, 7, 603-615.
208. Daoud, H.; Valdmanis, P. N.; Kabashi, E.; Dion, P.; Dupré, N.; Camu, W.; Meininger, V.; Rouleau, G. A. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J. Med. Genet., 2009, 46, 112-114.
209. Dewey, C. M.; Cenik, B.; Sephton, C. F.; Dries, D. R.; Mayer, P.; Good, S. K.; Johnson, B. A.; Herz, J.; Yu, G. TDP-43 Is Directed to Stress Granules by Sorbitol, a Novel Physiological Osmotic and Oxidative Stressor. Mol. Cell Biol., 2011, 31, 1098-1108.
210. Sama, R. R. K.; Ward, C. L.; Kaushansky, L. J.; Lemay, N.; Ishigaki, S.; Urano, F.; Bosco, D. A. FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress. J. Cell Physiol., 2013, 228, 2222-2231.
211. Sephton, C. F.; Cenik, C.; Kucukural, A.; Dammer, E. B.; Cenik, B.; Han, Y.; Dewey, C. M.; Roth, F. P.; Herz, J.; Peng, J.; Moore, M. J.; Yu, G. Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes. J. Biol. Chem., 2011, 286, 1204-1215.
212. Lagier-Tourenne, C.; Polymenidou, M.; Cleveland, D. W. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet., 2010, 19, R46-R64.
213. 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, 1205-1208.
214. Xu, Y.-F.; Zhang, Y.-J.; Lin, W.-L.; Cao, X.; Stetler, C.; Dickson, D.; Lewis, J.; Petrucelli, L. Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice. Molecular Neurodegeneration, 2011, 6, 73.
215. Wils, H.; Kleinberger, G.; Janssens, J.; Pereson, S.; Joris, G.; Cuijt, I.; Smits, V.; Ceuterick-de Groote, C.; Van Broeckhoven, C.; Kumar-Singh, S. TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Pro. Natl. Acad. Sci. USA, 2010, 107, 3858-3863.
216. Xu, Y.; Gendron, T.; Zhang, Y.; Lin, W.; D'Alton, S.; Sheng, H.; Casey, M.; Tong, J.; Knight, J.; Yu, X. Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J. Neurosci., 2010, 30, 10851-10859.
217. Igaz, L.; Kwong, L.; Lee, E.; Chen-Plotkin, A.; Swanson, E.; Unger, T.; Malunda, J.; Xu, Y.; Winton, M.; Trojanowski, J.; Lee, V. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J. Clin. Invest., 2011, 121, 726-738.
218. Shan, X.; Chiang, P.; Price, D.; Wong, P. Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc. Natl. Acad. Sci. USA, 2010, 107, 16325-16330.
219. Swarup, V.; Phaneuf, D.; Bareil, C.; Robertson, J.; Rouleau, G.; Kriz, J.; Julien, J. Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain, 2011, 134, 2610-2626.
220. Tsai, K.; Yang, C.; Fang, Y.; Cho, K.; Chien, W.; Wang, W.; Wu, T.; Lin, C.; Fu, W.; Shen, C. Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. J. Exp. Med., 2010, 207, 1661-1673.
221. Wegorzewska, I.; Bell, S.; Cairns, N.; Miller, T.; Baloh, R. TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc. Natl. Acad. Sci. USA, 2009, 106, 18809-18814.
222. 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-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol., 2008, 7, 409-416.
223. Wu, L. S.; Cheng, W. C.; Shen, C. K. Targeted depletion of TDP-43 expression in the spinal cord motor neurons leads to the development of amyotrophic lateral sclerosis-like phenotypes in mice. J. Biol. Chem., 2012, 287, 27335-27344.
224. Iguchi, Y.; Katsuno, M.; Niwa, J.-I.; Takagi, S.; Ishigaki, S.; Ikenaka, K.; Kawai, K.; Watanabe, H.; Yamanaka, K.; Takahashi, R.; Misawa, H.; Sasaki, S.; Tanaka, F.; Sobue, G. Loss of TDP-43 causes age-dependent progressive motor neuron degeneration. Brain, 2013, 136, 1371-1382.
225. Shelkovnikova, T. A.; Peters, O. M.; Deykin, A. V.; Connor-Robson, N.; Robinson, H.; Ustyugov, A. A.; Bachurin, S. O.; Ermolkevich, T. G.; Goldman, I. L.; Sadchikova, E. R.; Kovrazhkina, E. A.; Skvortsova, V. I.; Ling, S. C.; Da Cruz, S.; Parone, P. A.; Buchman, V. L.; Ninkina, N. N. Fused in Sarcoma (FUS) Protein Lacking Nuclear Localization Signal (NLS) and Major RNA Binding Motifs Triggers Proteinopathy and Severe Motor Phenotype in Transgenic Mice. J. Biol. Chem., 2013, 288, 25266-25274.
226. Murakami, T.; Yang, S. P.; Xie, L.; Kawano, T.; Fu, D.; Mukai, A.; Bohm, C.; Chen, F.; Robertson, J.; Suzuki, H.; Tartaglia, G. G.; Vendruscolo, M.; Kaminski Schierle, G. S.; Chan, F. T.; Moloney, A.; Crowther, D.; Kaminski, C. F.; Zhen, M.; St. George-Hyslop, P. ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism. Hum. Mol. Genet., 2012, 21, 1-9.
227. Colombrita, C.; Zennaro, E.; Fallini, C.; Weber, M.; Sommacal, A.; Buratti, E.; Silani, V.; Ratti, A. TDP-43 is recruited to stress granules in conditions of oxidative insult. J. Neurochem., 2009, 111, 1051-1061.
228. Andersson, M.; Stahlberg, A.; Arvidsson, Y.; Olofsson, A.; Semb, H.; Stenman, G.; Nilsson, O.; Aman, P. The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biology, 2008, 9, 37.
229. Liu-Yesucevitz, L.; Bilgutay, A.; Zhang, Y. J.; Vanderweyde, T.; Citro, A.; Mehta, T.; Zaarur, N.; McKee, A.; Bowser, R.; Sherman, M.; Petrucelli, L.; Wolozin, B. Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue. PLoS One, 2010, 5, e13250.
230. Ito, D.; Seki, M.; Tsunoda, Y.; Uchiyama, H.; Suzuki, N. Nuclear transport impairment of amyotrophic lateral sclerosis-linked mutations in FUS/TLS. Ann. Neurology, 2011, 69, 152-162.
231. Bosco, D. A.; Lemay, N.; Ko, H. K.; Zhou, H.; Burke, C.; Kwiatkowski, T. J.; Sapp, P.; McKenna-Yasek, D.; Brown, R. H.; Hayward, L. J. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum. Mol. Genet., 2010, 19, 4160-4175.
232. Bentmann, E.; Haass, C.; Dormann, D. Stress granules in neurodegeneration - lessons learnt from TAR DNA binding protein of 43 kDa and fused in sarcoma. FEBS J., 2013, 280, 4348-4370.
233. Dormann, D.; Rodde, R.; Edbauer, D.; Bentmann, E.; Fischer, I.; Hruscha, A.; Than, M. E.; Mackenzie, I. R. A.; Capell, A.; Schmid, B.; Neumann, M.; Haass, C. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J., 2010, 29, 2841-2857.
234. Dewey, C. M.; Cenik, B.; Sephton, C. F.; Johnson, B. A.; Herz, J.; Yu, G. TDP-43 aggregation in neurodegeneration: are stress granules the key? Brain Res., 2012, 1462, 16-25.
235. Siddique, T.; Figlewicz, D. A.; Pericak-Vance, M. A.; Haines, J. L.; Rouleau, G.; Jeffers, A. J.; Sapp, P.; Hung, W. Y.; Bebout, J.; McKenna-Yasek, D.; et al. Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N. Engl. J. Med., 1991, 324, 1381-1384.
236. Andersen, P. Amyotrophic lateral sclerosis genetics with Mendelian inheritance. In: Brown Jr R, Swash M, Pasinelli P, eds. Amyotrophic Lateral Sclerosis. 2nd ed. London: Informa Healthcare; 2006, 187-207.
237. Dewil, M.; Andersen, P.; Van Den Bosch, L.; Robberecht, W. Genetics of amyotrophic lateral sclerosis. In: Eisen A, Mauguiere F, eds. Clinical Neurophysiology of Motor Neuron Diseases. Amsterdam: Elsevier; 2004:169-86.
238. Robberecht, W. Genetics of familial amyotrophic lateral sclerosis and ethical aspects. In: Kuncl R, ed. Motor Neuron Disease. London: W. B. Saunders; 2002:75-95.
239. Levanon, D.; Lieman-Hurwitz, J.; Dafni, N.; Wigderson, M.; Sherman, L.; Bernstein, Y.; Laver-Rudich, Z.; Danciger, E.; Stein, O.; Groner, Y. Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase. EMBO J., 1985, 4, 77-84.
240. Fridovich, I. Superoxide dismutases. Adv Enzymol. Relat. Areas Mol. Biol., 1986, 58, 61-97.
241. Bowling, A. C.; Barkowski, E. E.; McKenna-Yasek, D.; Sapp, P.; Horvitz, H. R.; Beal, M. F.; Brown, R. H. Jr. Superoxide dismutase concentration and activity in familial amyotrophic lateral sclerosis. J. Neurochem., 1995, 64, 2366-2369.
242. Pardo, C. A.; Xu, Z.; Borchelt, D. R.; Price, D. L.; Sisodia, S. S.; Cleveland, D. W. Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. Proc. Natl. Acad. Sci. USA, 1995, 92, 954-958.
243. Cudkowicz, M. E.; McKenna-Yasek, D.; Sapp, P. E.; Chin, W.; Geller, B.; Hayden, D. L.; Schoenfeld, D. A.; Hosler, B. A.; Horvitz, H. R.; Brown, R. H. Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann. Neurol., 1997, 41, 210-221.
244. Orrell, R. W.; Habgood, J. J.; Gardiner, I.; King, A. W.; Bowe, F. A.; Hallewell, R. A.; Marklund, S. L.; Greenwood, J.; Lane, R. J.; Debelleroche, J. Clinical and functional investigation of 10 missense mutations and a novel frameshift insertion mutation of the gene for copper-zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis. Neurology, 1997, 48, 746-751.
245. 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, 390-394.
246. Juneja, T.; Pericak-Vance, M. A.; Laing, N. G.; Dave, S.; Siddique, T. Prognosis in familial amyotrophic lateral sclerosis: progression and survival in patients with glu100gly and ala4val mutations in Cu, Zn superoxide dismutase. Neurology, 1997, 48, 55-57.
247. Aoki, M.; Ogasawara, M.; Matsubara, Y.; Narisawa, K.; Nakamura, S.; Itoyama, Y.; Abe, K. Mild ALS in Japan associated with novel SOD mutation. Nat. Genet., 1993, 5, 323-324.
248. 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, 2045-2050.
249. Bruijn, L. I.; Beal, M. F.; Becher, M. W.; Schulz, J. B.; Wong, P. C.; Price, D. L.; Cleveland, D. W. Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant. Proc. Natl. Acad. Sci. USA, 1997, 94, 7606-7611.
250. Bruijn, L. I.; Houseweart, M. K.; Kato, S.; Anderson, K. L.; Anderson, S. D.; Ohama, E.; Reaume, A. G.; Scott, R. W.; Cleveland, D. W. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science, 1998, 281, 1851-1854.
251. Bruijn, L. I.; Miller, T. M.; Cleveland, D. W. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci., 2004, 27, 723-749.
252. Beckman, J. S.; Carson, M.; Smith, C. D.; Koppenol, W. H. ALS, SOD and peroxynitrite. Nature, 1993, 364, 584.
253. Andrus, P. K.; Fleck, T. J.; Gurney, M. E.; Hall, E. D. Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem., 1998, 71, 2041-2048.
254. Bogdanov, M. B.; Ramos, L. E.; Xu, Z.; Beal, M. F. Elevated "hydroxyl radical" generation in vivo in an animal model of amyotrophic lateral sclerosis. J. Neurochem., 1998, 71, 1321-1324.
255. Liu, R.; Althaus, J. S.; Ellerbrock, B. R.; Becker, D. A.; Gurney, M. E. Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann. Neurol., 1998, 44, 763-770.
256. Beckman, J. S.; Koppenol, W. H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol., 1996, 271, 1424-1437.
257. Crow, J. P.; Sampson, J. B.; Zhuang, Y.; Thompson, J. A.; Beckman, J. S. Decreased zinc affinity of amyotrophic lateral sclerosisassociated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J. Neurochem., 1997, 69, 1936-1944.
258. Abe, K.; Pan, L. H.; Watanabe, M.; Konno, H.; Kato, T.; Itoyama, Y. Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis. Neurol. Res., 1997, 19, 124-128.
259. Chou, S. M.; Wang, H. S.; Taniguchi, A. Role of SOD-1 and nitric oxide/cyclic GMP cascade on neurofilament aggregation in ALS/MND. J. Neurol. Sci., 1996, 139 Suppl, 16-26.
260. Beal, M. F.; Ferrante, R. J.; Browne, S. E.; Matthews, R. T.; Kowall, N. W.; Brown, R. H. Jr. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann. Neurol., 1997, 42, 644-654.
261. Ferrante, R. J.; Shinobu, L. A.; Schulz, J. B.; Matthews, R. T.; Thomas, C. E.; Kowall, N. W.; Gurney, M. E.; Beal, M. F. Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Ann. Neurol., 1997, 42, 326-334.
262. Hensley, K.; Mhatre, M.; Mou, S.; Pye, Q. N.; Stewart, C.; West, M.; Williamson, K. S. On the relation of oxidative stress to neuroinflammation: lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Antioxid. Redox. Signal., 2006, 8, 2075-2087.
263. Kim, Y. S.; Martinez, T.; Deshpande, D. M.; Drummond, J.; Provost-Javier, K.; Williams, A.; McGurk, J.; Maragakis, N.; Song, H.; Ming, G. L.; Kerr, D. A. Correction of humoral derangements from mutant superoxide dismutase 1 spinal cord. Ann. Neurol., 2006, 60, 716-728.
264. Estevez, A. G.; Crow, J. P.; Sampson, J. B.; Reiter, C.; Zhuang, Y.; Richardson, G. J.; Tarpey, M. M.; Barbeito, L.; Beckman, J. S. Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science, 1999, 286, 2498-2500.
265. Jonsson, P. A.; Graffmo, K. S.; Brannstrom, T.; Nilsson, P.; Andersen, P. M.; Marklund, S. L. Motor neuron disease in mice expressing the wild type-like D90A mutant superoxide dismutase-1. J. Neuropathol. Exp. Neurol., 2006, 65, 1126-1136.
266. Zetterstrom, P.; Stewart, H. G.; Bergemalm, D.; Jonsson, P. A.; Graffmo, K. S.; Andersen, P. M.; Brannstrom, T.; Oliveberg, M.; Marklund, S. L. Soluble misfolded subfractions of mutant superoxide dismutase-1s are enriched in spinal cords throughout life in murine ALS models. Proc. Natl. Acad. Sci. USA, 2007, 104, 14157-14162.
267. Williamson, T. L.; Cleveland, D. W. Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat. Neurosci., 1999, 2, 50-56.
268. Crooke, S. T. Progress in antisense technology. Annu. Rev. Med., 2004, 55, 61-95.