Amyotrophic Lateral Sclerosis

  • J. Jefferson P. Perry
  • David S. Shin
  • John A. Tainer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 685)


Amyotrophic lateral sclerosis (ALS) is a common neurological disorder that results in loss of motor neurons, leading to a rapidly progressive form of muscle paralysis that is fatal. There is no available cure and current therapies only provide minimal benefit at best. The disease is predominantly sporadic and until very recently only the Cu,Zn superoxide dismutase (Cu,ZnSOD), which is involved in a small number of sporadic cases and a larger component of familial ones, have been analyzed in any detail. Here we describe the clinical aspects of ALS and highlight the genetics and molecular mechanisms behind the disease. We discuss the current understanding and controversies of how mutations in Cu,ZnSOD may cause the disease. We also focus on the recent discovery that mutations in either TDP-43 or FUS/TLS, which are both involved in DNA/RNA synthesis, are likely the cause behind many cases of ALS that are not linked to Cu


Amyotrophic Lateral Sclerosis Motor Neuron Amyotrophic Lateral Sclerosis Patient Motor Neuron Disease Sporadic Amyotrophic Lateral Sclerosis 
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  1. 1.
    Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2001; 2(11):806–19.PubMedGoogle Scholar
  2. 2.
    Charcot JM. Deux cas d’atrophie musculaire progressive avec lesions de la substance grise et des faisceaux antero-lateraux de la moelle epiniere. Arch Physiol Neurol Pathol 1869: 2:744–54.Google Scholar
  3. 3.
    Traynor BJ, Codd MB, Corr B et al. Incidence and prevalence of ALS in Ireland, 1995–1997: a population-based study. Neurology 1999; 52(3):504–9.PubMedGoogle Scholar
  4. 4.
    Johnston CA, Stanton BR, Turner MR et al. Amyotrophic lateral sclerosis in an urban setting: a population based study of inner city London. J Neurol 2006; 253(12):1642–3.PubMedGoogle Scholar
  5. 5.
    Steele JC, McGeer PL. The ALS/PDC syndrome of Guam and the cycad hypothesis. Neurology 2008; 70(21):1984–90.PubMedGoogle Scholar
  6. 6.
    Ince PG, Codd GA. Return of the cycad hypothesis—does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health? Neuropathol Appl Neurobiol 2005; 31(4):345–53.PubMedGoogle Scholar
  7. 7.
    Haverkamp LJ, Appel V, Appel SH. Natural history of amyotrophic lateral sclerosis in a database population. Validation of a scoring system and a model for survival prediction. Brain 1995; 118(Pt 3):707–19.PubMedGoogle Scholar
  8. 8.
    Mulder DW, Kurland LT, Offord KP et al. Familial adult motor neuron disease: amyotrophic lateral sclerosis. Neurology 1986; 36(4):511–7.PubMedGoogle Scholar
  9. 9.
    Li TM, Alberman E, Swash M. Comparison of sporadic and familial disease amongst 580 cases of motor neuron disease. J Neurol Neurosurg Psychiatry 1988; 51(6):778–84.PubMedGoogle Scholar
  10. 10.
    Veltema AN, Roos RA, Bruyn GW. Autosomal dominant adult amyotrophic lateral sclerosis. A six generation Dutch family. J Neurol Sci 1990; 97(1):93–115.PubMedGoogle Scholar
  11. 11.
    Worms PM. The epidemiology of motor neuron diseases: a review of recent studies. J Neurol Sci 2001; 191(1–2):3–9.PubMedGoogle Scholar
  12. 12.
    Abhinav K, Stanton B, Johnston C et al. Amyotrophic lateral sclerosis in South-East England: a population-based study. The South-East England register for amyotrophic lateral sclerosis (SEALS Registry). Neuroepidemiology 2007; 29(1–2):44–8.PubMedGoogle Scholar
  13. 13.
    Zoccolella S, Beghi E, Palagano G et al. Analysis of survival and prognostic factors in amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 2008; 79(1):33–7.PubMedGoogle Scholar
  14. 14.
    Norris F, Shepherd R, Denys E et al. Onset, natural history and outcome in idiopathic adult motor neuron disease. J Neurol Sci 1993; 118(1):48–55.PubMedGoogle Scholar
  15. 15.
    Logroscino G, Traynor BJ, Hardiman O et al. Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry 2008; 79(1):6–11.PubMedGoogle Scholar
  16. 16.
    Testa D, Lovati R, Ferrarini M et al. Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 5(4):208–12.PubMedGoogle Scholar
  17. 17.
    Turner MR, Parton MJ, Shaw CE et al. Prolonged survival in motor neuron disease: a descriptive study of the King’s database 1990–2002. J Neurol Neurosurg Psychiatry 2003; 74(7):995–7.PubMedGoogle Scholar
  18. 18.
    Chio A, Benzi G, Dossena M et al. Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 2005; 128(Pt 3):472–6.PubMedGoogle Scholar
  19. 19.
    Weisskopf MG, McCullough ML, Calle EE et al. Prospective study of cigarette smoking and amyotrophic lateral sclerosis. Am J Epidemiol 2004; 160(1):26–33.PubMedGoogle Scholar
  20. 20.
    Fang F, Bellocco R, Hernan MA et al. Smoking, snuff dipping and the risk of amyotrophic lateral sclerosis-a prospective cohort study. Neuroepidemiology 2006; 27(4):217–21.PubMedGoogle Scholar
  21. 21.
    Horner RD, Grambow SC, Coffman CJ et al. Amyotrophic lateral sclerosis among 1991 Gulf War veterans: evidence for a time-limited outbreak. Neuroepidemiology 2008; 31(1):28–32.PubMedGoogle Scholar
  22. 22.
    Miranda ML, Alicia Overstreet Galeano M, Tassone E et al. Spatial analysis of the etiology of amyotrophic lateral sclerosis among 1991 Gulf War veterans. Neurotoxicology 2008; 29(6):964–70.PubMedGoogle Scholar
  23. 23.
    Beghi E, Millul A, Micheli A et al. Incidence of ALS in Lombardy, Italy. Neurology 2007; 68(2):141–5.PubMedGoogle Scholar
  24. 24.
    Forbes RB, Colville S, Swingler RJ. The epidemiology of amyotrophic lateral sclerosis (ALS/MND) in people aged 80 or over. Age Ageing 2004; 33(2):131–4.PubMedGoogle Scholar
  25. 25.
    Hayashi H, Kato S. Total manifestations of amyotrophic lateral sclerosis. ALS in the totally locked-in state. J Neurol Sci 1989; 93(1):19–35.PubMedGoogle Scholar
  26. 26.
    Sasaki S, Tsutsumi Y, Yamane K et al. Sporadic amyotrophic lateral sclerosis with extensive neurological involvement. Acta Neuropathol 1992; 84(2):211–5.PubMedGoogle Scholar
  27. 27.
    Miller RG, Mitchell JD, Lyon M et al. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2007(1):CD001447.Google Scholar
  28. 28.
    Distad BJ, Meekins GD, Liou LL et al. Drug therapy in amyotrophic lateral sclerosis. Phys Med Rehabil Clin N Am 2008; 19(3):633–51, xi-xii.PubMedGoogle Scholar
  29. 29.
    Piao YS, Wakabayashi K, Kakita A et al. Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. Brain Pathol 2003; 13(1):10–22.PubMedGoogle Scholar
  30. 30.
    Leigh PN, Dodson A, Swash M et al. Cytoskeletal abnormalities in motor neuron disease. An immunocytochemical study. Brain 1989; 112(Pt 2):521–35.PubMedGoogle Scholar
  31. 31.
    Rothstein JD, Tsai G, Kuncl RW et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990; 28(1):18–25.PubMedGoogle Scholar
  32. 32.
    Shaw PJ, Forrest V, Ince PG et al. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 1995; 4(2):209–16.PubMedGoogle Scholar
  33. 33.
    Nicholls DG, Budd SL. Mitochondria and neuronal survival. Physiol Rev 2000; 80(1):315–60.PubMedGoogle Scholar
  34. 34.
    Wiedemann FR, Winkler K, Kuznetsov AV et al. Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 1998; 156(1):65–72.PubMedGoogle Scholar
  35. 35.
    Dhaliwal GK, Grewal RP. Mitochondrial DNA deletion mutation levels are elevated in ALS brains. Neuroreport 2000; 11(11):2507–9.PubMedGoogle Scholar
  36. 36.
    Wiedemann FR, Manfredi G, Mawrin C et al. Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem 2002; 80(4):616–25.PubMedGoogle Scholar
  37. 37.
    Ro LS, Lai SL, Chen CM et al. Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic amyotrophic lateral sclerosis: a hospital-based case-control study. Muscle Nerve 2003; 28(6):737–43.PubMedGoogle Scholar
  38. 38.
    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(9):3241–50.PubMedGoogle Scholar
  39. 39.
    Krasnianski A, Deschauer M, Neudecker S et al. Mitochondrial changes in skeletal muscle in amyotrophic lateral sclerosis and other neurogenic atrophies. Brain 2005; 128(Pt 8):1870–6.PubMedGoogle Scholar
  40. 40.
    Ferri KF, Kroemer G. Mitochondria-the suicide organelles. Bioessays 2001; 23(2):111–5.PubMedGoogle Scholar
  41. 41.
    Guegan C, Przedborski S. Programmed cell death in amyotrophic lateral sclerosis. J Clin Invest 2003; 111(2):153–61.PubMedGoogle Scholar
  42. 42.
    Pasinelli P, Houseweart MK, Brown RH Jr et al. Caspase-1 and-3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2000; 97(25):13901–6.PubMedGoogle Scholar
  43. 43.
    Pasinelli P, Borchelt DR, Houseweart MK et al. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proc Natl Acad Sci USA 1998; 95(26):15763–8.PubMedGoogle Scholar
  44. 44.
    Vukosavic S, Dubois-Dauphin M, Romero N et al. Bax and Bcl-2 interaction in a transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 1999; 73(6):2460–8.PubMedGoogle Scholar
  45. 45.
    Li M, Ona VO, Guegan C et al. Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 2000; 288(5464):335–9.PubMedGoogle Scholar
  46. 46.
    Mitchell JD, Wokke JH, Borasio GD. Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2002(3):CD002064.Google Scholar
  47. 47.
    Bongioanni P, Reali C, Sogos V. Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/ motor neuron disease. Cochrane Database Syst Rev 2004(3):CD004302.Google Scholar
  48. 48.
    Ochs G, Penn RD, York M et al. A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1(3):201–6.PubMedGoogle Scholar
  49. 49.
    Meininger V, Bensimon G, Bradley WR et al. Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 5(2):107–17.PubMedGoogle Scholar
  50. 50.
    Hirano A, Donnenfeld H, Sasaki S et al. Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 1984; 43(5):461–70.PubMedGoogle Scholar
  51. 51.
    Ferrante RJ, Browne SE, Shinobu LA et al. Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J Neurochem 1997; 69(5):2064–74.PubMedGoogle Scholar
  52. 52.
    Smith RG, Henry YK, Mattson MP et al. Presence of 4-hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis. Ann Neurol 1998; 44(4):696–9.PubMedGoogle Scholar
  53. 53.
    Tohgi H, Abe T, Yamazaki K et al. Remarkable increase in cerebrospinal fluid 3-nitrotyrosine in patients with sporadic amyotrophic lateral sclerosis. Ann Neurol 1999; 46(1):129–31.PubMedGoogle Scholar
  54. 54.
    Tohgi H, Abe T, Yamazaki K et al. Increase in oxidized NO products and reduction in oxidized glutathione in cerebrospinal fluid from patients with sporadic form of amyotrophic lateral sclerosis. Neurosci Lett 1999; 260(3):204–6.PubMedGoogle Scholar
  55. 55.
    Rosen DR. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 364(6435):362.PubMedGoogle Scholar
  56. 56.
    Deng HX, Hentati A, Tainer JA et al. Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science 1993; 261(5124):1047–51.PubMedGoogle Scholar
  57. 57.
    Ben Hamida M, Hentati F, Ben Hamida C. Hereditary motor system diseases (chronic juvenile amyotrophic lateral sclerosis). Conditions combining a bilateral pyramidal syndrome with limb and bulbar amyotrophy. Brain 1990; 113(Pt 2):347–63.PubMedGoogle Scholar
  58. 58.
    Chance PF, Rabin BA, Ryan SG et al. Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. Am J Hum Genet 1998; 62(3):633–40.PubMedGoogle Scholar
  59. 59.
    Hentati A, Bejaoui K, Pericak-Vance MA et al. Linkage of recessive familial amyotrophic lateral sclerosis to chromosome 2q33-q35. Nat Genet 1994; 7(3):425–8.PubMedGoogle Scholar
  60. 60.
    Corrado L, Ratti A, Gellera C et al. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum Mutat 2009; 30(4):688–94.PubMedGoogle Scholar
  61. 61.
    Daoud H, Valdmanis PN, Kabashi E et al. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J Med Genet 2009; 46(2):112–4.PubMedGoogle Scholar
  62. 62.
    Gitcho MA, Baloh RH, Chakraverty S et al. TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 2008; 63(4):535–8.PubMedGoogle Scholar
  63. 63.
    Kabashi E, Valdmanis PN, Dion P et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 2008; 40(5):572–4.PubMedGoogle Scholar
  64. 64.
    Rutherford NJ, Zhang YJ, Baker M et al. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet 2008; 4(9):e1000193.PubMedGoogle Scholar
  65. 65.
    Sreedharan J, Blair IP, Tripathi VB et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319(5870):1668–72.PubMedGoogle Scholar
  66. 66.
    Van Deerlin VM, Leverenz JB, Bekris LM et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 2008; 7(5):409–16.PubMedGoogle Scholar
  67. 67.
    Kuhnlein P, Sperfeld AD, Vanmassenhove B et al. Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations. Arch Neurol 2008; 65(9):1185–9.PubMedGoogle Scholar
  68. 68.
    Kwiatkowski TJ Jr, Bosco DA, Leclerc AL et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009; 323(5918):1205–8.PubMedGoogle Scholar
  69. 69.
    Vance C, Rogelj B, Hortobagyi T et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009; 323(5918):1208–11.PubMedGoogle Scholar
  70. 70.
    Gaudette M, Hirano M, Siddique T. Current status of SOD1 mutations in familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1(2):83–9.PubMedGoogle Scholar
  71. 71.
    Wiedau-Pazos M, Goto JJ, Rabizadeh S et al. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science 1996; 271(5248):515–8.PubMedGoogle Scholar
  72. 72.
    Wanker EE. Protein aggregation in Huntington’s and Parkinson’s disease: implications for therapy. Mol Med Today 2000; 6(10):387–91.PubMedGoogle Scholar
  73. 73.
    Soto C. Protein misfolding and disease; protein refolding and therapy. FEBS Lett 2001; 498(2–3):204–7.PubMedGoogle Scholar
  74. 74.
    Dobson CM. Protein folding and its links with human disease. Biochem Soc Symp 2001(68):1–26.Google Scholar
  75. 75.
    Parge HE, Hallewell RA, Tainer JA. Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase. Proc Natl Acad Sci USA 1992; 89(13):6109–13.PubMedGoogle Scholar
  76. 76.
    Tainer JA, Getzoff ED, Beem KM et al. Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase. J Mol Biol 1982; 160(2):181–217.PubMedGoogle Scholar
  77. 77.
    Richardson JS. Beta-Sheet topology and the relatedness of proteins. Nature 1977; 268(5620): 495–500.PubMedGoogle Scholar
  78. 78.
    Hallewell RA, Imlay KC, Lee P et al. Thermostabilization of recombinant human and bovine CuZn superoxide dismutases by replacement of free cysteines. Biochem Biophys Res Commun 1991; 181(1):474–80.PubMedGoogle Scholar
  79. 79.
    Getzoff ED, Tainer JA, Stempien MM et al. Evolution of CuZn superoxide dismutase and the Greek key beta-barrel structural motif. Proteins 1989; 5(4):322–36.PubMedGoogle Scholar
  80. 80.
    Getzoff ED, Tainer JA, Weiner PK et al. Electrostatic recognition between superoxide and copper, zinc superoxide dismutase. Nature 1983; 306(5940):287–90.PubMedGoogle Scholar
  81. 81.
    Getzoff ED, Cabelli DE, Fisher CL et al. Faster superoxide dismutase mutants designed by enhancing electrostatic guidance. Nature 1992; 358(6384):347–51.PubMedGoogle Scholar
  82. 82.
    Shin DS, Didonato M, Barondeau DP et al. Superoxide dismutase from the eukaryotic thermophile Alvinella pompejana: structures, stability, mechanism and insights into amyotrophic lateral sclerosis. J Mol Biol 2009; 385(5):1534–55.PubMedGoogle Scholar
  83. 83.
    Bruijn LI, Houseweart MK, Kato S et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 1998; 281(5384):1851–4.PubMedGoogle Scholar
  84. 84.
    Durham HD, Roy J, Dong L et al. Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS. J Neuropathol Exp Neurol 1997; 56(5):523–30.PubMedGoogle Scholar
  85. 85.
    Johnston RB Jr, Godzik CA, Cohn ZA. Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 1978; 148(1):115–27.PubMedGoogle Scholar
  86. 86.
    DiDonato M, Craig L, Huff ME et al. ALS mutants of human superoxide dismutase form fibrous aggregates via framework destabilization. J Mol Biol 2003; 332(3):601–15.PubMedGoogle Scholar
  87. 87.
    Arai T, Hasegawa M, Akiyama H et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006; 351(3):602–11.PubMedGoogle Scholar
  88. 88.
    Neumann M, Sampathu DM, Kwong LK et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314(5796):130–3.PubMedGoogle Scholar
  89. 89.
    Talbot K, Ansorge O. Recent advances in the genetics of amyotrophic lateral sclerosis and frontotemporal dementia: common pathways in neurodegenerative disease. Hum Mol Genet 2006; 15 Spec No 2:R182–7.PubMedGoogle Scholar
  90. 90.
    Kwong LK, Uryu K, Trojanowski JQ et al. TDP-43 proteinopathies: neurodegenerative protein misfolding diseases without amyloidosis. Neurosignals 2008; 16(1):41–51.PubMedGoogle Scholar
  91. 91.
    Buratti E, Baralle FE. Multiple roles of TDP-43 in gene expression, splicing regulation and human disease. Front Biosci 2008; 13:867–78.PubMedGoogle Scholar
  92. 92.
    Ou SH, Wu F, Harrich D et al. Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J Virol 1995; 69(6):3584–96.PubMedGoogle Scholar
  93. 93.
    Abhyankar MM, Urekar C, Reddi PP. A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in somatic tissues: role for TDP-43 in insulator function. J Biol Chem 2007; 282(50):36143–54.PubMedGoogle Scholar
  94. 94.
    Ayala YM, Misteli T, Baralle FE. TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Proc Natl Acad Sci USA 2008; 105(10):3785–9.PubMedGoogle Scholar
  95. 95.
    Mantovani V, Garagnani P, Selva P et al. Simple method for haplotyping the poly(TG) repeat in individuals carrying the IVS8 5T allele in the CFTR gene. Clin Chem 2007; 53(3):531–3.PubMedGoogle Scholar
  96. 96.
    Strong MJ, Volkening K, Hammond R et al. TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci 2007; 35(2):320–7.PubMedGoogle Scholar
  97. 97.
    Wang IF, Wu LS, Chang HY et al. TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. J Neurochem 2008; 105(3):797–806.PubMedGoogle Scholar
  98. 98.
    Kuo PH, Doudeva LG, Wang YT et al. Structural insights into TDP-43 in nucleic-acid binding and domain interactions. Nucleic Acids Res 2009; 37(6):1799–808.PubMedGoogle Scholar
  99. 99.
    Yang X, Nagasaki K, Egawa S et al. FUS/TLS-CHOP chimeric transcripts in liposarcoma tissues. Jpn J Clin Oncol 1995; 25(6):234–9.PubMedGoogle Scholar
  100. 100.
    Mills KI, Walsh V, Gilkes AF et al. High FUS/TLS expression in acute myeloid leukaemia samples. Br J Haematol 2000; 108(2):316–21.PubMedGoogle Scholar
  101. 101.
    Perez-Losada J, Pintado B, Gutierrez-Adan A et al. The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice. Oncogene 2000; 19(20):2413–22.PubMedGoogle Scholar
  102. 102.
    Perez-Losada J, Sanchez-Martin M, Rodriguez-Garcia MA et al. Liposarcoma initiated by FUS/ TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma. Oncogene 2000; 19(52):6015–22.PubMedGoogle Scholar
  103. 103.
    Wang X, Arai S, Song X et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 2008; 454(7200):126–30.PubMedGoogle Scholar
  104. 104.
    Law WJ, Cann KL, Hicks GG. TLS, EWS and TAF15: a model for transcriptional integration of gene expression. Brief Funct Genomic Proteomic 2006; 5(1):8–14.PubMedGoogle Scholar
  105. 105.
    Cassiday LA, Maher LJ, 3rd. Having it both ways: transcription factors that bind DNA and RNA. Nucleic Acids Res 2002; 30(19):4118–26.PubMedGoogle Scholar
  106. 106.
    Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43. Cell 2009; 136(6):1001–4.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • J. Jefferson P. Perry
    • 1
    • 2
  • David S. Shin
    • 1
  • John A. Tainer
    • 1
  1. 1.Department of Molecular BiologyThe Scripps Research InstituteLa JollaUSA
  2. 2.The School of BiotechnologyAmrita UniversityKeralaIndia

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