Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis;¿Por qué degeneran las motoneuronas? Actualización en la patogenia de la esclerosis lateral amiotrófica

Neurologia

Volumn 34, Issue 1, 2019, Pages 27-37

  Riancho, J ^a,c   Gonzalo, I ^b   Ruiz Soto, M ^b,c   Berciano, J ^a,c  

^a HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA   (Spain)

^b UNIVERSITY OF CANTABRIA   (Spain)

^c CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED SOBRE ENFERMEDADES NEURODEGENERATIVAS CIBERNED   (Spain)

Author keywords

Amyotrophic lateral sclerosis; Motor neuron; Neurodegeneration

Indexed keywords

PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; BRAIN NERVE CELL; HUMAN; MOTONEURON; NERVE FIBER TRANSPORT; OXIDATIVE STRESS; PATHOGENESIS; PROTEIN METABOLISM; SHORT SURVEY; ANIMAL; DISEASE MODEL; GENETICS; METABOLISM; PATHOLOGY;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; MOTOR NEURONS;

EID: 84974526160     PISSN: 02134853     EISSN: 15781968     Source Type: Journal    
DOI: 10.1016/j.nrl.2015.12.001     Document Type: Short Survey

References (114)

1. Lopez-Vega, J.M., Calleja, J., Combarros, O., Polo, J.M., Berciano, J., Motor neuron disease in Cantabria. Acta Neurol Scand 77 (1988), 1–5.
2. a ed., 2008, Elsevier, Madrid.
3. Amato, A., Russell, J., Neuromuscular disorders. 2008, McGraw Hill, China.
4. Ferraiuolo, L., Kirby, J., Grierson, A.J., Sendtner, M., Shaw, P.J., Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat Rev Neurol 7 (2011), 616–630.
5. Schymick, J.C., Talbot, K., Traynor, B.J., Genetics of sporadic amyotrophic lateral sclerosis. Hum Mol Genet 2:16 Spec No. (2007), R233–R242.
6. Dunckley, T., Huentelman, M.J., Craig, D.W., Pearson, J.V., Szelinger, S., Joshipura, K., et al. Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N Engl J Med 357 (2007), 775–788.
7. Van Es, M.A., van Vught, P.W., Blauw, H.M., Franke, L., Saris, C.G., van Den, B.L., et al. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nat Genet 40 (2008), 29–31.
8. Van Es, M.A., van Vught, P.W., Blauw, H.M., Franke, L., Saris, C.G., Andersen, P.M., et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 6 (2007), 869–877.
9. Ahmeti, K.B., Ajroud-Driss, S., Al Chalabi, A., Andersen, P.M., Armstrong, J., Birve, A., et al. Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1. Neurobiol Aging 34 (2013), 357–419.
10. DeJesus-Hernandez, M., Mackenzie, I.R., Boeve, B.F., Boxer, A.L., Baker, M., Rutherford, N.J., et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72 (2011), 245–256.
11. Renton, A.E., Majounie, E., Waite, A., Simon-Sanchez, J., Rollinson, S., Gibbs, J.R., et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72 (2011), 257–268.
12. Byrne, S., Elamin, M., Bede, P., Shatunov, A., Walsh, C., Corr, B., et al. Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study. Lancet Neurol 11 (2012), 232–240.
13. Van Rheenen, W., van Blitterswijk, M., Huisman, M.H., Vlam, L., van Doormaal, P.T., Seelen, M., et al. Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases. Neurology 79 (2012), 878–882.
14. Alexander, M.D., Traynor, B.J., Miller, N., Corr, B., Frost, E., McQuaid, S., et al. «True» sporadic ALS associated with a novel SOD-1 mutation. Ann Neurol 52 (2002), 680–683.
15. Chio, A., Calvo, A., Moglia, C., Ossola, I., Brunetti, M., Sbaiz, L., et al. A de novo missense mutation of the FUS gene in a «true» sporadic ALS case. Neurobiol Aging 32 (2011), 553–556.
16. Chesi, A., Staahl, B.T., Jovicic, A., Couthouis, J., Fasolino, M., Raphael, A.R., et al. Exome sequencing to identify de novo mutations in sporadic ALS trios. Nat Neurosci 16 (2013), 851–855.
17. Lefebvre, S., Burglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80 (1995), 155–165.
18. Burghes, A.H., Beattie, C.E., Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?. Nat Rev Neurosci 10 (2009), 597–609.
19. Fallini, C., Bassell, G.J., Rossoll, W., Spinal muscular atrophy: the role of SMN in axonal mRNA regulation. Brain Res 1462 (2012), 81–92.
20. Rutherford, N.J., Zhang, Y.J., Baker, M., Gass, J.M., Finch, N.A., Xu, Y.F., et al. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet, 4, 2008, e1000193.
21. Mackenzie, I.R., Rademakers, R., Neumann, M., TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 9 (2010), 995–1007.
22. Lee, E.B., Lee, V.M., Trojanowski, J.Q., Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat Rev Neurosci 13 (2012), 38–50.
23. Andersen, P.M., Al Chalabi, A., Clinical genetics of amyotrophic lateral sclerosis: what do we really know?. Nat Rev Neurol 7 (2011), 603–615.
24. Dewey, C.M., Cenik, B., Sephton, C.F., Dries, D.R., Mayer, P. III, Good, S.K., et al. TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor. Mol Cell Biol 31 (2011), 1098–1108.
25. Shorter, J., The mammalian disaggregase machinery: Hsp110 synergizes with Hsp70 and Hsp40 to catalyze protein disaggregation and reactivation in a cell-free system. PLoS One, 6, 2011, e26319.
26. Tollervey, J.R., Curk, T., Rogelj, B., Briese, M., Cereda, M., Kayikci, M., et al. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 14 (2011), 452–458.
27. Johnson, B.S., Snead, D., Lee, J.J., McCaffery, J.M., Shorter, J., Gitler, A.D., TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 284 (2009), 20329–20339.
28. Bertolotti, A., Lutz, Y., Heard, D.J., Chambon, P., Tora, L., hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. EMBO J 15 (1996), 5022–5031.
29. Ito, D., Seki, M., Tsunoda, Y., Uchiyama, H., Suzuki, N., Nuclear transport impairment of amyotrophic lateral sclerosis-linked mutations in FUS/TLS. Ann Neurol 69 (2011), 152–162.
30. Dormann, D., Rodde, R., Edbauer, D., Bentmann, E., Fischer, I., Hruscha, A., et al. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J 29 (2010), 2841–2857.
31. Lagier-Tourenne, C., Polymenidou, M., Hutt, K.R., Vu, A.Q., Baughn, M., Huelga, S.C., et al. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci 15 (2012), 1488–1497.
32. Majounie, E., Renton, A.E., Mok, K., Dopper, E.G., Waite, A., Rollinson, S., et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11 (2012), 323–330.
33. Levine, T.P., Daniels, R.D., Gatta, A.T., Wong, L.H., Hayes, M.J., The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs. Bioinformatics 29 (2013), 499–503.
34. Marat, A.L., Dokainish, H., McPherson, P.S., DENN domain proteins: regulators of Rab GTPases. J Biol Chem 286 (2011), 13791–13800.
35. Gijselinck, I., van Langenhove, T., van der, Z.J., Sleegers, K., Philtjens, S., Kleinberger, G., et al. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol 11 (2012), 54–65.
36. Greenway, M.J., Andersen, P.M., Russ, C., Ennis, S., Cashman, S., Donaghy, C., et al. ANG mutations segregate with familial and 'sporadic’ amyotrophic lateral sclerosis. Nat Genet 38 (2006), 411–413.
37. Saxena, S., Caroni, P., Selective neuronal vulnerability in neurodegenerative diseases: from stressor thresholds to degeneration. Neuron 71 (2011), 35–48.
38. Kusaka, H., Imai, T., Hashimoto, S., Yamamoto, T., Maya, K., Yamasaki, M., Ultrastructural study of chromatolytic neurons in an adult-onset sporadic case of amyotrophic lateral sclerosis. Acta Neuropathol 75 (1988), 523–528.
39. Martin, L.J., Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J Neuropathol Exp Neurol 58 (1999), 459–471.
40. Oyanagi, K., Yamazaki, M., Takahashi, H., Watabe, K., Wada, M., Komori, T., et al. Spinal anterior horn cells in sporadic amyotrophic lateral sclerosis show ribosomal detachment from, and cisternal distention of the rough endoplasmic reticulum. Neuropathol Appl Neurobiol 34 (2008), 650–658.
41. Sasaki, S., Endoplasmic reticulum stress in motor neurons of the spinal cord in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 69 (2010), 346–355.
42. Raska, I., Shaw, P.J., Cmarko, D., New insights into nucleolar architecture and activity. Int Rev Cytol 255 (2006), 177–235.
43. Boisvert, F.M., van Koningsbruggen, S., Navascues, J., Lamond, A.I., The multifunctional nucleolus. Nat Rev Mol Cell Biol 8 (2007), 574–585.
44. Grummt, I., The nucleolus-guardian of cellular homeostasis and genome integrity. Chromosoma 122 (2013), 487–497.
45. Olson, M.O., Sensing cellular stress: another new function for the nucleolus?. Sci STKE, 2004, 2004, e10.
46. Boulon, S., Westman, B.J., Hutten, S., Boisvert, F.M., Lamond, A.I., The nucleolus under stress. Mol Cell 40 (2010), 216–227.
47. Kreiner, G., Bierhoff, H., Armentano, M., Rodriguez-Parkitna, J., Sowodniok, K., Naranjo, J.R., et al. A neuroprotective phase precedes striatal degeneration upon nucleolar stress. Cell Death Differ 20 (2013), 1455–1464.
48. Parlato, R., Liss, B., How Parkinson's disease meets nucleolar stress. Biochim Biophys Acta 1842 (2014), 791–797.
49. Hetman, M., Vashishta, A., Rempala, G., Neurotoxic mechanisms of DNA damage: focus on transcriptional inhibition. J Neurochem 114 (2010), 1537–1549.
50. Baltanas, F.C., Casafont, I., Weruaga, E., Alonso, J.R., Berciano, M.T., Lafarga, M., Nucleolar disruption and cajal body disassembly are nuclear hallmarks of DNA damage-induced neurodegeneration in purkinje cells. Brain Pathol 21 (2011), 374–388.
51. Hetman, M., Pietrzak, M., Emerging roles of the neuronal nucleolus. Trends Neurosci 35 (2012), 305–314.
52. Parlato, R., Kreiner, G., Nucleolar activity in neurodegenerative diseases: a missing piece of the puzzle?. J Mol Med (Berl) 91 (2013), 541–547.
53. Lee, J., Hwang, Y.J., Ryu, H., Kowall, N.W., Ryu, H., Nucleolar dysfunction in Huntington's disease. Biochim Biophys Acta 1842 (2014), 785–790.
54. Riancho, J., Ruiz-Soto, M., T.Villagrá, N., Berciano, J., Berciano, M.T., Lafarga, M., Compensatory motor neuron response to chromatolysis in the murine hSOD1 G93A model of amyotrophic lateral sclerosis. Front Cell Neurosci, 2014, 8.
55. Gary, J.D., Sato, T.K., Stefan, C.J., Bonangelino, C.J., Weisman, L.S., Emr, S.D., Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by Vac7 protein and Fig4, a polyphosphoinositide phosphatase family member. Mol Biol Cell 13 (2002), 1238–1251.
56. Ko, H.S., Uehara, T., Tsuruma, K., Nomura, Y., Ubiquilin interacts with ubiquitylated proteins and proteasome through its ubiquitin-associated and ubiquitin-like domains. FEBS Lett 566:1–3 (2004), 110–114.
57. Bertram, L., Hiltunen, M., Parkinson, M., Ingelsson, M., Lange, C., Ramasamy, K., et al. Family-based association between Alzheimer's disease and variants in UBQLN1. N Engl J Med 352 (2005), 884–894.
58. Williams, K.L., Warraich, S.T., Yang, S., Solski, J.A., Fernando, R., Rouleau, G.A., et al. UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis. Neurobiol Aging 33 (2012), 2527–2610.
59. Johnson, J.O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V.M., Trojanowski, J.Q., et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68 (2010), 857–864.
60. Ritson, G.P., Custer, S.K., Freibaum, B.D., Guinto, J.B., Geffel, D., Moore, J., et al. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J Neurosci 30 (2010), 7729–7739.
61. Song, C., Wang, Q., Li, C.C., ATPase activity of p97-valosin-containing protein (VCP). D2 mediates the major enzyme activity, and D1 contributes to the heat-induced activity. J Biol Chem 278 (2003), 3648–3655.
62. Parkinson, N., Ince, P.G., Smith, M.O., Highley, R., Skibinski, G., Andersen, P.M., et al. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2 B). Neurology 67 (2006), 1074–1077.
63. Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465 (2010), 223–226.
64. Chow, C.Y., Landers, J.E., Bergren, S.K., Sapp, P.C., Grant, A.E., Jones, J.M., et al. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am J Hum Genet 84 (2009), 85–88.
65. Filimonenko, M., Stuffers, S., Raiborg, C., Yamamoto, A., Malerod, L., Fisher, E.M., et al. Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol 179 (2007), 485–500.
66. Kachaner, D., Genin, P., Laplantine, E., Weil, R., Toward an integrative view of Optineurin functions. Cell Cycle 11 (2012), 2808–2818.
67. Albagha, O.M., Visconti, M.R., Alonso, N., Langston, A.L., Cundy, T., Dargie, R., et al. Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone. Nat Genet 42 (2010), 520–524.
68. Bendotti, C., Marino, M., Cheroni, C., Fontana, E., Crippa, V., Poletti, A., et al. Dysfunction of constitutive and inducible ubiquitin-proteasome system in amyotrophic lateral sclerosis: implication for protein aggregation and immune response. Prog Neurobiol 97 (2012), 101–126.
69. Chen, S., Zhang, X., Song, L., Le, W., Autophagy dysregulation in amyotrophic lateral sclerosis. Brain Pathol 22 (2012), 110–116.
70. Morimoto, N., Nagai, M., Ohta, Y., Miyazaki, K., Kurata, T., Morimoto, M., et al. Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. Brain Res 1167 (2007), 112–117.
71. Sasaki, S., Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 70 (2011), 349–359.
72. Robberecht, W., Philips, T., The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 14 (2013), 248–264.
73. Ezzi, S.A., Urushitani, M., Julien, J.P., Wild-type superoxide dismutase acquires binding and toxic properties of ALS-linked mutant forms through oxidation. J Neurochem 102 (2007), 170–178.
74. Bosco, D.A., Morfini, G., Karabacak, N.M., Song, Y., Gros-Louis, F., Pasinelli, P., et al. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci 13 (2010), 1396–1403.
75. Smith, R.G., Henry, Y.K., Mattson, M.P., Appel, S.H., Presence of 4-hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis. Ann Neurol 44 (1998), 696–699.
76. Simpson, E.P., Henry, Y.K., Henkel, J.S., Smith, R.G., Appel, S.H., Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden. Neurology 62 (2004), 1758–1765.
77. Mitsumoto, H., Santella, R.M., Liu, X., Bogdanov, M., Zipprich, J., Wu, H.C., et al. Oxidative stress biomarkers in sporadic ALS. Amyotroph Lateral Scler 9 (2008), 177–183.
78. Shaw, P.J., Ince, P.G., Falkous, G., Mantle, D., Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol 38 (1995), 691–695.
79. Shibata, N., Nagai, R., Uchida, K., Horiuchi, S., Yamada, S., Hirano, A., et al. Morphological evidence for lipid peroxidation and protein glycoxidation in spinal cords from sporadic amyotrophic lateral sclerosis patients. Brain Res 917 (2001), 97–104.
80. Fitzmaurice, P.S., Shaw, I.C., Kleiner, H.E., Miller, R.T., Monks, T.J., Lau, S.S., et al. Evidence for DNA damage in amyotrophic lateral sclerosis. Muscle Nerve 19 (1996), 797–798.
81. Graham, D., Lantos, P., Greenfield's Neuropathology. 7. th ed., 2002, Arnold, London.
82. Tashiro, Y., Urushitani, M., Inoue, H., Koike, M., Uchiyama, Y., Komatsu, M., et al. Motor neuron-specific disruption of proteasomes, but not autophagy, replicates amyotrophic lateral sclerosis. J Biol Chem 287 (2012), 42984–42994.
83. De Vos, K.J., Chapman, A.L., Tennant, M.E., Manser, C., Tudor, E.L., Lau, K.F., et al. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 16 (2007), 2720–2728.
84. Vinsant, S., Mansfield, C., Jimenez-Moreno, R., del, G.M., Yoshikawa, V.M., Hampton, T.G., et al. Characterization of early pathogenesis in the SOD1(G93A) mouse model of ALS: part II, results and discussion. Brain Behav 3 (2013), 431–457.
85. Vinsant, S., Mansfield, C., Jimenez-Moreno, R., del Gaizo Moore, V., Yoshikawa, M., Hampton, T.G., et al. Characterization of early pathogenesis in the SOD1(G93A) mouse model of ALS: part I, background and methods. Brain Behav 3 (2013), 335–350.
86. Miller, K.E., Sheetz, M.P., Axonal mitochondrial transport and potential are correlated. J Cell Sci 117:Pt 13 (2004), 2791–2804.
87. Kiaei, M., Kipiani, K., Calingasan, N.Y., Wille, E., Chen, J., Heissig, B., et al. Matrix metalloproteinase-9 regulates TNF-alpha and FasL expression in neuronal, glial cells and its absence extends life in a transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol 205 (2007), 74–81.
88. Ackerley, S., Grierson, A.J., Brownlees, J., Thornhill, P., Anderton, B.H., Leigh, P.N., et al. Glutamate slows axonal transport of neurofilaments in transfected neurons. J Cell Biol 150 (2000), 165–176.
89. Bergeron, C., Beric-Maskarel, K., Muntasser, S., Weyer, L., Somerville, M.J., Percy, M.E., Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J Neuropathol Exp Neurol 53 (1994), 221–230.
90. Volkening, K., Leystra-Lantz, C., Yang, W., Jaffee, H., Strong, M.J., Tar DNA binding protein of 43 kDa (TDP-43), 14-3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain Res 1305 (2009), 168–182.
91. Wu, C.H., Fallini, C., Ticozzi, N., Keagle, P.J., Sapp, P.C., Piotrowska, K., et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488 (2012), 499–503.
92. Figlewicz, D.A., Krizus, A., Martinoli, M.G., Meininger, V., Dib, M., Rouleau, G.A., et al. Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet 3 (1994), 1757–1761.
93. Gros-Louis, F., Lariviere, R., Gowing, G., Laurent, S., Camu, W., Bouchard, J.P., et al. A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J Biol Chem 279 (2004), 45951–45956.
94. Puls, I., Jonnakuty, C., LaMonte, B.H., Holzbaur, E.L., Tokito, M., Mann, E., et al. Mutant dynactin in motor neuron disease. Nat Genet 33 (2003), 455–456.
95. Yang, Y., Hentati, A., Deng, H.X., Dabbagh, O., Sasaki, T., Hirano, M., et al. The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet 29 (2001), 160–165.
96. Ruiz, DA, Fabre, P.J., Knevels, E., Coulon, C., Segura, I., Haddick, P.C., et al. VEGF mediates commissural axon chemoattraction through its receptor Flk1. Neuron 70 (2011), 966–978.
97. Storkebaum, E., Lambrechts, D., Dewerchin, M., Moreno-Murciano, M.P., Appelmans, S., Oh, H., et al. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat Neurosci 8 (2005), 85–92.
98. Landers, J.E., Melki, J., Meininger, V., Glass, J.D., van den Berg, L.H., van Es, M.A., et al. Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 106 (2009), 9004–9009.
99. Van Es, M.A., Veldink, J.H., Saris, C.G., Blauw, H.M., van Vught, P.W., Birve, A., et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet 41 (2009), 1083–1087.
100. Van Damme, P., Dewil, M., Robberecht, W., van Den, B.L., Excitotoxicity and amyotrophic lateral sclerosis. Neurodegener Dis 2:3–4 (2005), 147–159.
101. Carriedo, S.G., Yin, H.Z., Weiss, J.H., Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J Neurosci 16 (1996), 4069–4079.
102. Williams, T.L., Day, N.C., Ince, P.G., Kamboj, R.K., Shaw, P.J., Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis. Ann Neurol 42 (1997), 200–207.
103. Shaw, P.J., Forrest, V., Ince, P.G., Richardson, J.P., Wastell, H.J., CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 4 (1995), 209–216.
104. Rothstein, J.D., Martin, L.J., Kuncl, R.W., Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326 (1992), 1464–1468.
105. Vucic, S., Nicholson, G.A., Kiernan, M.C., Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain 131:Pt 6 (2008), 1540–1550.
106. Kwak, S., Hideyama, T., Yamashita, T., Aizawa, H., AMPA receptor-mediated neuronal death in sporadic ALS. Neuropathology 30 (2010), 182–188.
107. Henkel, J.S., Engelhardt, J.I., Siklos, L., Simpson, E.P., Kim, S.H., Pan, T., et al. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol 55 (2004), 221–235.
108. Yamanaka, K., Chun, S.J., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann, D.H., et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11 (2008), 251–253.
109. Boillee, S., Vande, V.C., Cleveland, D.W., ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 52 (2006), 39–59.
110. Kuhle, J., Lindberg, R.L., Regeniter, A., Mehling, M., Steck, A.J., Kappos, L., et al. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol 16 (2009), 771–774.
111. Hensley, K., Abdel-Moaty, H., Hunter, J., Mhatre, M., Mou, S., Nguyen, K., et al. Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation. J Neuroinflammation, 3, 2006, 2.
112. Haidet-Phillips, A.M., Hester, M.E., Miranda, C.J., Meyer, K., Braun, L., Frakes, A., et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 29 (2011), 824–828.
113. Lee, Y., Morrison, B.M., Li, Y., Lengacher, S., Farah, M.H., Hoffman, P.N., et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487 (2012), 443–448.
114. Philips, T., Bento-Abreu, A., Nonneman, A., Haeck, W., Staats, K., Geelen, V., et al. Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis. Brain 136:Pt 2 (2013), 471–482.