TDP-43/FUS in motor neuron disease: Complexity and challenges

Progress in Neurobiology

Volumn 145-146, Issue , 2016, Pages 78-97

  Guerrero, Erika N ^a,b,c   Wang, Haibo ^a   Mitra, Joy ^a   Hegde, Pavana M ^a   Stowell, Sara E ^d   Liachko, Nicole F ^e   Kraemer, Brian C ^e   Garruto, Ralph M ^d   Rao, K S ^b,c   Hegde, Muralidhar L ^a,f  

^a HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^b INSTITUTO DE INVESTIGACIONES CIENTÍFICAS Y SERVICIOS DE ALTA TECNOLOGÍA   (Panama)

^c ACHARYA NAGARJUNA UNIVERSITY   (India)

^d BINGHAMTON UNIVERSITY   (United States)

^e VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^f WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Amyotrophic lateral sclerosis; FUS TLS; Genome damage repair; RNA processing; TDP 43

Indexed keywords

ATAXIN 2; DNA; FUSED IN SARCOMA PROTEIN; HETEREOGENEOUS RIBONUCLEOPROTEIN HARBOR PRION LIKE DOMAIN A1; HETEREOGENEOUS RIBONUCLEOPROTEIN HARBOR PRION LIKE DOMAIN A2 B1; NEK 1 KINASE; OPTONEURIN; TAR DNA BINDING PROTEIN; UBIQUILIN 2; UNCLASSIFIED DRUG; VALOSIN CONTAINING PROTEIN; DNA BINDING PROTEIN; FUS PROTEIN, HUMAN; RNA BINDING PROTEIN FUS; TDP-43 PROTEIN, HUMAN;

AMYOTROPHIC LATERAL SCLEROSIS; DISEASE COURSE; DNA DAMAGE; DNA REPAIR; FRONTOTEMPORAL DEMENTIA; GENOME; MOTONEURON; MOTOR NEURON DISEASE; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN METHYLATION; PROTEIN PHOSPHORYLATION; REVIEW; UBIQUITINATION; GENETICS; HUMAN;

AMYOTROPHIC LATERAL SCLEROSIS; DNA-BINDING PROTEINS; HUMANS; RNA-BINDING PROTEIN FUS;

EID: 84994201669     PISSN: 03010082     EISSN: 18735118     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2016.09.004     Document Type: Review

References (295)

1. Abhyankar, M.M., Urekar, C., Reddi, P.P., A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in somatic tissues: role for TDP-43 in insulator function. J. Biol. Chem. 282 (2007), 36143–36154.
2. Acevedo-Arozena, A., Kalmar, B., Essa, S., Ricketts, T., Joyce, P., Kent, R., Rowe, C., Parker, A., Gray, A., Hafezparast, M., Thorpe, J.R., Greensmith, L., Fisher, E.M., A comprehensive assessment of the SOD1G93A low-copy transgenic mouse, which models human amyotrophic lateral sclerosis. Dis. Model Mech. 4 (2011), 686–700.
3. Acosta, J.R., Goldsbury, C., Winnick, C., Badrock, A.P., Fraser, S.T., Laird, A.S., Hall, T.E., Don, E.K., Fifita, J.A., Blair, I.P., Nicholson, G.A., Cole, N.J., Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells. PLoS One, 9, 2014, e90572.
4. Al-Chalabi, A., Jones, A., Troakes, C., King, A., Al-Sarraj, S., van den Berg, L.H., The genetics and neuropathology of amyotrophic lateral sclerosis. Acta Neuropathol. 124 (2012), 339–352.
5. Al-Sarraj, S., King, A., Troakes, C., Smith, B., Maekawa, S., Bodi, I., Rogelj, B., Al-Chalabi, A., Hortobagyi, 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. Acta Neuropathol. 122 (2011), 691–702.
6. Aman, P., Panagopoulos, I., Lassen, C., Fioretos, T., Mencinger, M., Toresson, H., Hoglund, M., Forster, A., Rabbitts, T.H., Ron, D., Mandahl, N., Mitelman, F., Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. Genomics 37 (1996), 1–8.
7. Andersen, P.M., Al-Chalabi, A., Clinical genetics of amyotrophic lateral sclerosis: what do we really know?. Nat. Rev. Neurol. 7 (2011), 603–615.
8. Andersson, M.K., 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 Biol., 9, 2008, 37.
9. Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., Oda, T., TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351 (2006), 602–611.
10. Arif, M., Kazim, S.F., Grundke-Iqbal, I., Garruto, R.M., Iqbal, K., Tau pathology involves protein phosphatase 2A in parkinsonism-dementia of Guam. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 1144–1149.
11. Arnold, E.S., Ling, S.C., Huelga, S.C., Lagier-Tourenne, C., Polymenidou, M., Ditsworth, D., Kordasiewicz, H.B., McAlonis-Downes, M., Platoshyn, O., Parone, P.A., Da Cruz, S., Clutario, K.M., Swing, D., Tessarollo, L., Marsala, M., Shaw, C.E., Yeo, G.W., Cleveland, D.W., ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), E736–745.
12. Ash, P.E., Zhang, Y.J., Roberts, C.M., Saldi, T., Hutter, H., Buratti, E., Petrucelli, L., Link, C.D., Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum. Mol. Genet. 19 (2010), 3206–3218.
13. Aulas, A., Stabile, S., Vande Velde, C., Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP. Mol. Neurodegener., 7, 2012, 54.
14. Avendano-Vazquez, S.E., Dhir, A., Bembich, S., Buratti, E., Proudfoot, N., Baralle, F.E., Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection. Genes Dev. 26 (2012), 1679–1684.
15. Ayala, Y.M., Pantano, S., D'Ambrogio, A., Buratti, E., Brindisi, A., Marchetti, C., Romano, M., Baralle, F.E., Human, Drosophila, and C. elegans TDP43: nucleic acid binding properties and splicing regulatory function. J. Mol. Biol. 348 (2005), 575–588.
16. Ayala, Y.M., Misteli, T., Baralle, F.E., TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 3785–3789.
17. Ayala, Y.M., Zago, P., D'Ambrogio, A., Xu, Y.F., Petrucelli, L., Buratti, E., Baralle, F.E., Structural determinants of the cellular localization and shuttling of TDP-43. J. Cell Sci. 121 (2008), 3778–3785.
18. Ayala, Y.M., De Conti, L., Avendano-Vazquez, S.E., Dhir, A., Romano, M., D'Ambrogio, A., Tollervey, J., Ule, J., Baralle, M., Buratti, E., Baralle, F.E., TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J. 30 (2011), 277–288.
19. Baechtold, H., Kuroda, M., Sok, J., Ron, D., Lopez, B.S., Akhmedov, A.T., Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation. J. Biol. Chem. 274 (1999), 34337–34342.
20. Bakkar, N., Kousari, A., Kovalik, T., Li, Y., Bowser, R., RBM45 modulates the antioxidant response in amyotrophic lateral sclerosis through interactions with KEAP1. Mol. Cell. Biol. 35 (2015), 2385–2399.
21. Baron, D.M., Kaushansky, L.J., Ward, C.L., Sama, R.R., Chian, R.J., Boggio, K.J., Quaresma, A.J., Nickerson, J.A., Bosco, D.A., Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics. Mol. Neurodegener., 8, 2013, 30.
22. Belly, A., Moreau-Gachelin, F., Sadoul, R., Goldberg, Y., Delocalization of the multifunctional RNA splicing factor TLS/FUS in hippocampal neurones: exclusion from the nucleus and accumulation in dendritic granules and spine heads. Neurosci. Lett. 379 (2005), 152–157.
23. Beltran, M., Puig, I., Pena, C., Garcia, J.M., Alvarez, A.B., Pena, R., Bonilla, F., de Herreros, A.G., A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 22 (2008), 756–769.
24. Benajiba, L., Le Ber, I., Camuzat, A., Lacoste, M., Thomas-Anterion, C., Couratier, P., Legallic, S., Salachas, F., Hannequin, D., Decousus, M., Lacomblez, L., Guedj, E., Golfier, V., Camu, W., Dubois, B., Campion, D., Meininger, V., Brice, A., French, C., Genetic Research Network on Frontotemporal Lobar Degeneration/Frontotemporal Lobar Degeneration with Motoneuron, D.,. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann. Neurol. 65 (2009), 470–473.
25. 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 81 (2010), 639–645.
26. Blokhuis, A.M., Groen, E.J., Koppers, M., van den Berg, L.H., Pasterkamp, R.J., Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol. 125 (2013), 777–794.
27. Borghero, G., Floris, G., Cannas, A., Marrosu, M.G., Murru, M.R., Costantino, E., Parish, L.D., Pugliatti, M., Ticca, A., Traynor, B.J., Calvo, A., Cammarosano, S., Moglia, C., Cistaro, A., Brunetti, M., Restagno, G., Chio, A., A patient carrying a homozygous p. A382T TARDBP missense mutation shows a syndrome including ALS, extrapyramidal symptoms, and FTD. Neurobiol. Aging 32:2327 (2011), e2321–e2325.
28. Borroni, B., Bonvicini, C., Alberici, A., Buratti, E., Agosti, C., Archetti, S., Papetti, A., Stuani, C., Di Luca, M., Gennarelli, M., Padovani, A., Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum. Mutat. 30 (2009), E974–983.
29. Bosco, D.A., Lemay, N., Ko, H.K., Zhou, H., Burke, C., Kwiatkowski, T.J. Jr., Sapp, P., McKenna-Yasek, D., Brown, R.H. Jr., Hayward, L.J., Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum. Mol. Genet. 19 (2010), 4160–4175.
30. Boxer, A.L., Mackenzie, I.R., Boeve, B.F., Baker, M., Seeley, W.W., Crook, R., Feldman, H., Hsiung, G.Y., Rutherford, N., Laluz, V., Whitwell, J., Foti, D., McDade, E., Molano, J., Karydas, A., Wojtas, A., Goldman, J., Mirsky, J., Sengdy, P., Dearmond, S., Miller, B.L., Rademakers, R., Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J. Neurol. Neurosurg. Psychiatry 82 (2011), 196–203.
31. Bradley, W.G., Krasin, F., A new hypothesis of the etiology of amyotrophic lateral sclerosis. The DNA hypothesis. Arch. Neurol. 39 (1982), 677–680.
32. Broustal, O., Camuzat, A., Guillot-Noel, L., Guy, N., Millecamps, S., Deffond, D., Lacomblez, L., Golfier, V., Hannequin, D., Salachas, F., Camu, W., Didic, M., Dubois, B., Meininger, V., Le Ber, I., Brice, A., French, C., Genetic Research Network on, F. F.-M, FUS mutations in frontotemporal lobar degeneration with amyotrophic lateral sclerosis. J. Alzheimers Dis. 22 (2010), 765–769.
33. Brouwers, N., Bettens, K., Gijselinck, I., Engelborghs, S., Pickut, B.A., Van Miegroet, H., Montoya, A.G., Mattheijssens, M., Peeters, K., De Deyn, P.P., Cruts, M., Sleegers, K., Van Broeckhoven, C., Contribution of TARDBP to Alzheimer's disease genetic etiology. J. Alzheimers Dis. 21 (2010), 423–430.
34. Buratti, E., Baralle, F.E., Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J. Biol. Chem. 276 (2001), 36337–36343.
35. Buratti, E., Baralle, F.E., TDP-43: new aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease. FEBS J. 278 (2011), 3530–3538.
36. Buratti, E., Dork, T., Zuccato, E., Pagani, F., Romano, M., Baralle, F.E., Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J. 20 (2001), 1774–1784.
37. Burd, C.G., Dreyfuss, G., Conserved structures and diversity of functions of RNA-binding proteins. Science 265 (1994), 615–621.
38. Calvio, C., Neubauer, G., Mann, M., Lamond, A.I., Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry. RNA 1 (1995), 724–733.
39. Cannas, A., Borghero, G., Floris, G.L., Solla, P., Chio, A., Traynor, B.J., Calvo, A., Restagno, G., Majounie, E., Costantino, E., Piras, V., Lavra, L., Pani, C., Orofino, G., Di Stefano, F., Tacconi, P., Mascia, M.M., Muroni, A., Murru, M.R., Tranquilli, S., Corongiu, D., Rolesu, M., Cuccu, S., Marrosu, F., Marrosu, M.G., The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms. Neurogenetics 14 (2013), 161–166.
40. Caragounis, A., Price, K.A., Soon, C.P., Filiz, G., Masters, C.L., Li, Q.X., Crouch, P.J., White, A.R., Zinc induces depletion and aggregation of endogenous TDP-43. Free Radic. Biol. Med. 48 (2010), 1152–1161.
41. Casafont, I., Bengoechea, R., Tapia, O., Berciano, M.T., Lafarga, M., TDP-43 localizes in mRNA transcription and processing sites in mammalian neurons. J. Struct. Biol. 167 (2009), 235–241.
42. Chen, Y., Chen, C.F., Riley, D.J., Chen, P.L., Nek1 kinase functions in DNA damage response and checkpoint control through a pathway independent of ATM and ATR. Cell Cycle 10 (2011), 655–663.
43. Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R., TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436 (2005), 740–744.
44. Chiang, P.M., Ling, J., Jeong, Y.H., Price, D.L., Aja, S.M., Wong, P.C., Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 16320–16324.
45. Chiang, H.H., Andersen, P.M., Tysnes, O.B., Gredal, O., Christensen, P.B., Graff, C., Novel TARDBP mutations in Nordic ALS patients. J. Hum. Genet. 57 (2012), 316–319.
46. Chio, A., Calvo, A., Ilardi, A., Cavallo, E., Moglia, C., Mutani, R., Palmo, A., Galletti, R., Marinou, K., Papetti, L., Mora, G., Lower serum lipid levels are related to respiratory impairment in patients with ALS. Neurology 73 (2009), 1681–1685.
47. Chio, A., Restagno, G., Brunetti, M., Ossola, I., Calvo, A., Mora, G., Sabatelli, M., Monsurro, M.R., Battistini, S., Mandrioli, J., Salvi, F., Spataro, R., Schymick, J., Traynor, B.J., La Bella, V., Consortium, I., Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation. Neurobiol. Aging 30 (2009), 1272–1275.
48. Chio, A., Calvo, A., Moglia, C., Restagno, G., Ossola, I., Brunetti, M., Montuschi, A., Cistaro, A., Ticca, A., Traynor, B.J., Schymick, J.C., Mutani, R., Marrosu, M.G., Murru, M.R., Borghero, G., Amyotrophic lateral sclerosis-frontotemporal lobar dementia in 3 families with p.Ala382Thr TARDBP mutations. Arch. Neurol. 67 (2010), 1002–1009.
49. Chio, A., Logroscino, G., Traynor, B.J., Collins, J., Simeone, J.C., Goldstein, L.A., White, L.A., Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 41 (2013), 118–130.
50. Cohen, T.J., Hwang, A.W., Unger, T., Trojanowski, J.Q., Lee, V.M., Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking. EMBO J. 31 (2012), 1241–1252.
51. Cohen, T.J., Hwang, A.W., Restrepo, C.R., Yuan, C.X., Trojanowski, J.Q., Lee, V.M., An acetylation switch controls TDP-43 function and aggregation propensity. Nat. Commun., 6, 2015, 5845.
52. Collins, M., Riascos, D., Kovalik, T., An, J., Krupa, K., Krupa, K., Hood, B.L., Conrads, T.P., Renton, A.E., Traynor, B.J., Bowser, R., The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) patients. Acta Neuropathol. 124 (2012), 717–732.
53. Coppede, F., An overview of DNA repair in amyotrophic lateral sclerosis. Sci. World J. 11 (2011), 1679–1691.
54. Corrado, L., Ratti, A., Gellera, C., Buratti, E., Castellotti, B., Carlomagno, Y., Ticozzi, N., Mazzini, L., Testa, L., Taroni, F., Baralle, F.E., Silani, V., D'Alfonso, S., High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum. Mutat. 30 (2009), 688–694.
55. Correia, A.S., Patel, P., Dutta, K., Julien, J.P., Inflammation induces TDP-43 mislocalization and aggregation. PLoS One, 10, 2015, e0140248.
56. Cox, P.A., Sacks, O.W., Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology 58 (2002), 956–959.
57. Cozzolino, M., Carri, M.T., Mitochondrial dysfunction in ALS. Prog. Neurobiol. 97 (2012), 54–66.
58. Cushman, M., Johnson, B.S., King, O.D., Gitler, A.D., Shorter, J., Prion-like disorders: blurring the divide between transmissibility and infectivity. J. Cell Sci. 123 (2010), 1191–1201.
59. de Lau, L.M., Breteler, M.M., Epidemiology of Parkinson's disease. Lancet Neurol. 5 (2006), 525–535.
60. D'Ambrogio, A., Buratti, E., Stuani, C., Guarnaccia, C., Romano, M., Ayala, Y.M., Baralle, F.E., Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo. Nucl. Acids Res. 37 (2009), 4116–4126.
61. Daoud, H., Valdmanis, P.N., Kabashi, E., Dion, P., Dupre, N., Camu, W., Meininger, V., Rouleau, G.A., Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J. Med. Genet. 46 (2009), 112–114.
62. DeJesus-Hernandez, M., Mackenzie, I.R., Boeve, B.F., Boxer, A.L., Baker, M., Rutherford, N.J., Nicholson, A.M., Finch, N.A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G.Y., Karydas, A., Seeley, W.W., Josephs, K.A., Coppola, G., Geschwind, D.H., Wszolek, Z.K., Feldman, H., Knopman, D.S., Petersen, R.C., Miller, B.L., Dickson, D.W., Boylan, K.B., Graff-Radford, N.R., Rademakers, R., Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72 (2011), 245–256.
63. Del Bo, R., Ghezzi, S., Corti, S., Pandolfo, M., Ranieri, M., Santoro, D., Ghione, I., Prelle, A., Orsetti, V., Mancuso, M., Soraru, G., Briani, C., Angelini, C., Siciliano, G., Bresolin, N., Comi, G.P., TARDBP (TDP-43) sequence analysis in patients with familial and sporadic ALS: identification of two novel mutations. Eur. J. Neurol. 16 (2009), 727–732.
64. Deng, H.X., Zhai, H., Bigio, E.H., Yan, J., Fecto, F., Ajroud, K., Mishra, M., Ajroud-Driss, S., Heller, S., Sufit, R., Siddique, N., Mugnaini, E., Siddique, T., FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann. Neurol. 67 (2010), 739–748.
65. Deng, H.X., Bigio, E.H., Zhai, H., Fecto, F., Ajroud, K., Shi, Y., Yan, J., Mishra, M., Ajroud-Driss, S., Heller, S., Sufit, R., Siddique, N., Mugnaini, E., Siddique, T., Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations. Arch. Neurol. 68 (2011), 1057–1061.
66. Deng, H.X., Chen, W., Hong, S.T., Boycott, K.M., Gorrie, G.H., Siddique, N., Yang, Y., Fecto, F., Shi, Y., Zhai, H., Jiang, H., Hirano, M., Rampersaud, E., Jansen, G.H., Donkervoort, S., Bigio, E.H., Brooks, B.R., Ajroud, K., Sufit, R.L., Haines, J.L., Mugnaini, E., Pericak-Vance, M.A., Siddique, T., Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477 (2011), 211–215.
67. Deng, H., Gao, K., Jankovic, J., The role of FUS gene variants in neurodegenerative diseases. Nat. Rev. Neurol. 10 (2014), 337–348.
68. Deng, Q., Holler, C.J., Taylor, G., Hudson, K.F., Watkins, W., Gearing, M., Ito, D., Murray, M.E., Dickson, D.W., Seyfried, N.T., Kukar, T., FUS is phosphorylated by DNA-PK and accumulates in the cytoplasm after DNA damage. J Neurosci. 34 (2014), 7802–7813.
69. Dewey, C.M., Cenik, B., Sephton, C.F., Dries, D.R., Mayer, P. 3rd, 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. 31 (2011), 1098–1108.
70. Dormann, D., Haass, C., TDP-43 and FUS: a nuclear affair. Trends Neurosci. 34 (2011), 339–348.
71. Dormann, D., Haass, C., Fused in sarcoma (FUS): an oncogene goes awry in neurodegeneration. Mol. Cell Neurosci. 56 (2013), 475–486.
72. Dormann, D., Rodde, R., Edbauer, D., Bentmann, E., Fischer, I., Hruscha, A., Than, M.E., Mackenzie, I.R., Capell, A., Schmid, B., Neumann, M., Haass, C., ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J. 29 (2010), 2841–2857.
73. Dormann, D., Madl, T., Valori, C.F., Bentmann, E., Tahirovic, S., Abou-Ajram, C., Kremmer, E., Ansorge, O., Mackenzie, I.R., Neumann, M., Haass, C., Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. EMBO J. 31 (2012), 4258–4275.
74. Dreyfuss, G., Matunis, M.J., Pinol-Roma, S., Burd, C.G., hnRNP proteins and the biogenesis of mRNA. Annu. Rev. Biochem. 62 (1993), 289–321.
75. Du, K., Arai, S., Kawamura, T., Matsushita, A., Kurokawa, R., TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation. Biochem. Biophys. Res. Commun. 404 (2011), 991–996.
76. Elden, A.C., Kim, H.J., Hart, M.P., Chen-Plotkin, A.S., Johnson, B.S., Fang, X., Armakola, M., Geser, F., Greene, R., Lu, M.M., Padmanabhan, A., Clay-Falcone, D., McCluskey, L., Elman, L., Juhr, D., Gruber, P.J., Rub, U., Auburger, G., Trojanowski, J.Q., Lee, V.M., Van Deerlin, V.M., Bonini, N.M., Gitler, A.D., Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466 (2010), 1069–1075.
77. Esmaeili, M.A., Panahi, M., Yadav, S., Hennings, L., Kiaei, M., Premature death of TDP-43 (A315T) transgenic mice due to gastrointestinal complications prior to development of full neurological symptoms of amyotrophic lateral sclerosis. Int. J. Exp. Pathol. 94 (2013), 56–64.
78. Farg, M.A., Soo, K.Y., Warraich, S.T., Sundaramoorthy, V., Blair, I.P., Atkin, J.D., Ataxin-2 interacts with FUS and intermediate-length polyglutamine expansions enhance FUS-related pathology in amyotrophic lateral sclerosis. Hum. Mol. Genet. 22 (2013), 717–728.
79. Fay, R.M., Walker, C.S., Powers, J.M., Discoloration of a compomer by stains. J. Gt. Houst. Dent. Soc. 69 (1998), 12–13.
80. Feiguin, F., Godena, V.K., Romano, G., D'Ambrogio, A., Klima, R., Baralle, F.E., Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior. FEBS Lett. 583 (2009), 1586–1592.
81. 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.
82. Fiesel, F.C., Voigt, A., Weber, S.S., Van den Haute, C., Waldenmaier, A., Gorner, K., Walter, M., Anderson, M.L., Kern, J.V., Rasse, T.M., Schmidt, T., Springer, W., Kirchner, R., Bonin, M., Neumann, M., Baekelandt, V., Alunni-Fabbroni, M., Schulz, J.B., Kahle, P.J., Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. EMBO J. 29 (2010), 209–221.
83. Filimonenko, M., Stuffers, S., Raiborg, C., Yamamoto, A., Malerod, L., Fisher, E.M., Isaacs, A., Brech, A., Stenmark, H., Simonsen, A., Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J. Cell Biol. 179 (2007), 485–500.
84. Freibaum, B.D., Lu, Y., Lopez-Gonzalez, R., Kim, N.C., Almeida, S., Lee, K.H., Badders, N., Valentine, M., Miller, B.L., Wong, P.C., Petrucelli, L., Kim, H.J., Gao, F.B., Taylor, J.P., GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525 (2015), 129–133.
85. Fridovich, I., The biology of oxygen radicals. Science 201 (1978), 875–880.
86. Fujii, R., Okabe, S., Urushido, T., Inoue, K., Yoshimura, A., Tachibana, T., Nishikawa, T., Hicks, G.G., Takumi, T., The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. Curr. Biol. 15 (2005), 587–593.
87. Gal, J., Zhang, J., Kwinter, D.M., Zhai, J., Jia, H., Jia, J., Zhu, H., Nuclear localization sequence of FUS and induction of stress granules by ALS mutants. Neurobiol. Aging 32:2323 (2011), e2327–e2340.
88. Gardiner, M., Toth, R., Vandermoere, F., Morrice, N.A., Rouse, J., Identification and characterization of FUS/TLS as a new target of ATM. Biochem. J. 415 (2008), 297–307.
89. Garruto, R.M., Gajdusek, C., Chen, K.M., Amyotrophic lateral sclerosis among Chamorro migrants from Guam. Ann. Neurol. 8 (1980), 612–619.
90. Garruto, R.M., Gajdusek, D.C., Chen, K.M., Amyotrophic lateral sclerosis and parkinsonism-dementia among Filipino migrants to Guam. Ann. Neurol. 10 (1981), 341–350.
91. Garruto, R.M., Swyt, C., Fiori, C.E., Yanagihara, R., Gajdusek, D.C., Intraneuronal deposition of calcium and aluminium in amyotropic lateral sclerosis of Guam. Lancet, 2, 1985, 1353.
92. Garruto, R.M., Yanagihara, R., Gajdusek, D.C., Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam. Neurology 35 (1985), 193–198.
93. Garruto, R.M., Pacific paradigms of environmentally-induced neurological disorders: clinical, epidemiological and molecular perspectives. Neurotoxicology 12 (1991), 347–377.
94. Gendron, T.F., Rademakers, R., Petrucelli, L., TARDBP mutation analysis in TDP-43 proteinopathies and deciphering the toxicity of mutant TDP-43. J. Alzheimers Dis. 33:Suppl. 1 (2013), S35–45.
95. Geser, F., Winton, M.J., Kwong, L.K., Xu, Y., Xie, S.X., Igaz, L.M., Garruto, R.M., Perl, D.P., Galasko, D., Lee, V.M., Trojanowski, J.Q., Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Acta Neuropathol. 115 (2008), 133–145.
96. Gilks, N., Kedersha, N., Ayodele, M., Shen, L., Stoecklin, G., Dember, L.M., Anderson, P., Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol. Biol Cell. 15 (2004), 5383–5398.
97. Gitcho, M.A., Baloh, R.H., Chakraverty, S., Mayo, K., Norton, J.B., Levitch, D., Hatanpaa, K.J., White, C.L. 3rd, Bigio, E.H., Caselli, R., Baker, M., Al-Lozi, M.T., Morris, J.C., Pestronk, A., Rademakers, R., Goate, A.M., Cairns, N.J., TDP-43 A315T mutation in familial motor neuron disease. Ann. Neurol. 63 (2008), 535–538.
98. Gitcho, M.A., Strider, J., Carter, D., Taylor-Reinwald, L., Forman, M.S., Goate, A.M., Cairns, N.J., VCP mutations causing frontotemporal lobar degeneration disrupt localization of TDP-43 and induce cell death. J. Biol. Chem. 284 (2009), 12384–12398.
99. Gitler, A.D., Shorter, J., RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion 5 (2011), 179–187.
100. Gregory, R.I., Chendrimada, T.P., Cooch, N., Shiekhattar, R., Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123 (2005), 631–640.
101. Gunnarsson, L.G., Dahlbom, K., Strandman, E., Motor neuron disease and dementia reported among 13 members of a single family. Acta Neurol. Scand. 84 (1991), 429–433.
102. Guo, Y., Wang, Q., Zhang, K., An, T., Shi, P., Li, Z., Duan, W., Li, C., HO-1 induction in motor cortex and intestinal dysfunction in TDP-43 A315T transgenic mice. Brain Res. 1460 (2012), 88–95.
103. Hallier, M., Lerga, A., Barnache, S., Tavitian, A., Moreau-Gachelin, F., The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS. J. Biol. Chem. 273 (1998), 4838–4842.
104. Han, J.H., Yu, T.H., Ryu, H.H., Jun, M.H., Ban, B.K., Jang, D.J., Lee, J.A., ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons. Exp. Cell Res. 319 (2013), 1998–2005.
105. Hans, F., Fiesel, F.C., Strong, J.C., Jackel, S., Rasse, T.M., Geisler, S., Springer, W., Schulz, J.B., Voigt, A., Kahle, P.J., UBE2E ubiquitin-conjugating enzymes and ubiquitin isopeptidase Y regulate TDP-43 protein ubiquitination. J. Biol. Chem. 289 (2014), 19164–19179.
106. Hanson, K.A., Kim, S.H., Wassarman, D.A., Tibbetts, R.S., Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral sclerosis (ALS). J. Biol. Chem. 285 (2010), 11068–11072.
107. Hart, M.P., Gitler, A.D., ALS-associated ataxin 2 polyQ expansions enhance stress-induced caspase 3 activation and increase TDP-43 pathological modifications. J. Neurosci. 32 (2012), 9133–9142.
108. Hasegawa, M., Arai, T., Akiyama, H., Nonaka, T., Mori, H., Hashimoto, T., Yamazaki, M., Oyanagi, K., TDP-43 is deposited in the Guam parkinsonism-dementia complex brains. Brain 130 (2007), 1386–1394.
109. 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. 64 (2008), 60–70.
110. Hebert, L.E., Weuve, J., Scherr, P.A., Evans, D.A., Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology 80 (2013), 1778–1783.
111. Hebron, M.L., Lonskaya, I., Sharpe, K., Weerasinghe, P.P., Algarzae, N.K., Shekoyan, A.R., Moussa, C.E., Parkin ubiquitinates Tar-DNA binding protein-43 (TDP-43) and promotes its cytosolic accumulation via interaction with histone deacetylase 6 (HDAC6). J. Biol. Chem. 288 (2013), 4103–4115.
112. Hegde, M.L., Mantha, A.K., Hazra, T.K., Bhakat, K.K., Mitra, S., Szczesny, B., Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases. Mech. Ageing Dev. 133 (2012), 157–168.
113. Hicks, G.G., Singh, N., Nashabi, A., Mai, S., Bozek, G., Klewes, L., Arapovic, D., White, E.K., Koury, M.J., Oltz, E.M., Van Kaer, L., Ruley, H.E., Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nat. Genet. 24 (2000), 175–179.
114. Hoffman, P.M., Robbins, D.S., Gibbs, C.J. Jr., Gajdusek, D.C., Garruto, R.M., Terasaki, O.I., Histocompatibility antigens in amyotrophic lateral sclerosis and parkinsonism-dementia on Guam. Lancet, 2, 1977, 717.
115. Holcik, M., Sonenberg, N., Translational control in stress and apoptosis. Nat. Rev. Mol. Cell. Biol. 6 (2005), 318–327.
116. Honda, D., Ishigaki, S., Iguchi, Y., Fujioka, Y., Udagawa, T., Masuda, A., Ohno, K., Katsuno, M., Sobue, G., The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons. FEBS Open Bio 4 (2013), 1–10.
117. Honda, H., Hamasaki, H., Wakamiya, T., Koyama, S., Suzuki, S.O., Fujii, N., Iwaki, T., Loss of hnRNPA1 in ALS spinal cord motor neurons with TDP-43-positive inclusions. Neuropathology 35 (2015), 37–43.
118. Hortobagyi, T., Troakes, C., Nishimura, A.L., Vance, C., van Swieten, J.C., Seelaar, H., King, A., Al-Sarraj, S., Rogelj, B., Shaw, C.E., Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders. Acta Neuropathol. 121 (2011), 519–527.
119. Huey, E.D., Ferrari, R., Moreno, J.H., Jensen, C., Morris, C.M., Potocnik, F., Kalaria, R.N., Tierney, M., Wassermann, E.M., Hardy, J., Grafman, J., Momeni, P., FUS and TDP43 genetic variability in FTD and CBS. Neurobiol Aging 33:1016 (2012), e1017–e1019.
120. Ichikawa, H., Shimizu, K., Hayashi, Y., Ohki, M., An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res. 54 (1994), 2865–2868.
121. Igaz, L.M., Kwong, L.K., Lee, E.B., Chen-Plotkin, A., Swanson, E., Unger, T., Malunda, J., Xu, Y., Winton, M.J., Trojanowski, J.Q., Lee, V.M., Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J. Clin. Invest. 121 (2011), 726–738.
122. Iguchi, Y., Katsuno, M., Niwa, J., 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 136 (2013), 1371–1382.
123. Iko, Y., Kodama, T.S., Kasai, N., Oyama, T., Morita, E.H., Muto, T., Okumura, M., Fujii, R., Takumi, T., Tate, S., Morikawa, K., Domain architectures and characterization of an RNA-binding protein, TLS. J. Biol. Chem. 279 (2004), 44834–44840.
124. Ishiura, H., Takahashi, Y., Mitsui, J., Yoshida, S., Kihira, T., Kokubo, Y., Kuzuhara, S., Ranum, L.P., Tamaoki, T., Ichikawa, Y., Date, H., Goto, J., Tsuji, S., C9ORF72 repeat expansion in amyotrophic lateral sclerosis in the Kii peninsula of Japan. Arch. Neurol. 69 (2012), 1154–1158.
125. 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.
126. Jackel, S., Summerer, A.K., Thommes, C.M., Pan, X., Voigt, A., Schulz, J.B., Rasse, T.M., Dormann, D., Haass, C., Kahle, P.J., Nuclear import factor transportin and arginine methyltransferase 1 modify FUS neurotoxicity in Drosophila. Neurobiol. Dis. 74 (2015), 76–88.
127. Jackson, K.L., Dayton, R.D., Orchard, E.A., Ju, S., Ringe, D., Petsko, G.A., Maquat, L.E., Klein, R.L., Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther. 22 (2015), 20–28.
128. Janssens, J., Wils, H., Kleinberger, G., Joris, G., Cuijt, I., Ceuterick-de Groote, C., Van Broeckhoven, C., Kumar-Singh, S., Overexpression of ALS-associated p. M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice. Mol. Neurobiol. 48 (2013), 22–35.
129. Johnson, J.O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V.M., Trojanowski, J.Q., Gibbs, J.R., Brunetti, M., Gronka, S., Wuu, J., Ding, J., McCluskey, L., Martinez-Lage, M., Falcone, D., Hernandez, D.G., Arepalli, S., Chong, S., Schymick, J.C., Rothstein, J., Landi, F., Wang, Y.D., Calvo, A., Mora, G., Sabatelli, M., Monsurro, M.R., Battistini, S., Salvi, F., Spataro, R., Sola, P., Borghero, G., Consortium, I., Galassi, G., Scholz, S.W., Taylor, J.P., Restagno, G., Chio, A., Traynor, B.J., Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68 (2010), 857–864.
130. Kabashi, E., Valdmanis, P.N., Dion, P., Spiegelman, D., McConkey, B.J., Vande Velde, C., Bouchard, J.P., Lacomblez, L., Pochigaeva, K., Salachas, F., Pradat, P.F., Camu, W., Meininger, V., Dupre, N., Rouleau, G.A., TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40 (2008), 572–574.
131. Kabashi, E., Bercier, V., Lissouba, A., Liao, M., Brustein, E., Rouleau, G.A., Drapeau, P., FUS and TARDBP but not SOD1 interact in genetic models of amyotrophic lateral sclerosis. PLoS Genet., 7, 2011, e1002214.
132. Kabashi, E., Brustein, E., Champagne, N., Drapeau, P., Zebrafish models for the functional genomics of neurogenetic disorders. Biochim. Biophys. Acta 1812 (2011), 335–345.
133. Kabuta, C., Kono, K., Wada, K., Kabuta, T., 4-Hydroxynonenal induces persistent insolubilization of TDP-43 and alters its intracellular localization. Biochem. Biophys. Res. Commun. 463 (2015), 82–87.
134. Kang, L., Liu, X., Gong, Z., Zheng, H., Wang, J., Li, Y., Yang, H., Hardwick, J., Dai, H., Poon, R.T., Lee, N.P., Mao, M., Peng, Z., Chen, R., Genome-wide identification of RNA editing in hepatocellular carcinoma. Genomics 105 (2015), 76–82.
135. Kawahara, Y., Mieda-Sato, A., TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 3347–3352.
136. Kawamata, T., Akiyama, H., Yamada, T., McGeer, P.L., Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am. J. Pathol. 140 (1992), 691–707.
137. Kedersha, N., Anderson, P., Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem. Soc. Trans. 30 (2002), 963–969.
138. Keller, B.A., Volkening, K., Droppelmann, C.A., Ang, L.C., Rademakers, R., Strong, M.J., Co-aggregation of RNA binding proteins in ALS spinal motor neurons: evidence of a common pathogenic mechanism. Acta Neuropathol. 124 (2012), 733–747.
139. Kenna, K.P., van Doormaal, P.T., Dekker, A.M., Ticozzi, N., Kenna, B.J., Diekstra, F.P., van Rheenen, W., van Eijk, K.R., Jones, A.R., Keagle, P., Shatunov, A., Sproviero, W., Smith, B.N., van Es, M.A., Topp, S.D., Kenna, A., Miller, J.W., Fallini, C., Tiloca, C., McLaughlin, R.L., Vance, C., Troakes, C., Colombrita, C., Mora, G., Calvo, A., Verde, F., Al-Sarraj, S., King, A., Calini, D., de Belleroche, J., Baas, F., van der Kooi, A.J., de Visser, M., Ten Asbroek, A.L., Sapp, P.C., McKenna-Yasek, D., Polak, M., Asress, S., Munoz-Blanco, J.L., Strom, T. M., Meitinger, T., Morrison, K.E., Consortium, S., Lauria, G., Williams, K.L., Leigh, P.N., Nicholson, G.A., Blair, I.P., Leblond, C.S., Dion, P.A., Rouleau, G.A., Pall, H., Shaw, P.J., Turner, M.R., Talbot, K., Taroni, F., Boylan, K.B., Van Blitterswijk, M., Rademakers, R., Esteban-Perez, J., Garcia-Redondo, A., Van Damme, P., Robberecht, W., Chio, A., Gellera, C., Drepper, C., Sendtner, M., Ratti, A., Glass, J.D., Mora, J.S., Basak, N.A., Hardiman, O., Ludolph, A.C., Andersen, P.M., Weishaupt, J.H., Brown, R.H., Jr., Al-Chalabi, A., Silani, V., Shaw, C.E., van den Berg, L.H., Veldink, J.H., Landers, J.E., 2016. NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nat Genet. in press.
140. Kim, S.H., Shanware, N.P., Bowler, M.J., Tibbetts, R.S., Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA. J. Biol. Chem. 285 (2010), 34097–34105.
141. Kim, H.J., Kim, N.C., Wang, Y.D., Scarborough, E.A., Moore, J., Diaz, Z., MacLea, K.S., Freibaum, B., Li, S., Molliex, A., Kanagaraj, A.P., Carter, R., Boylan, K.B., Wojtas, A.M., Rademakers, R., Pinkus, J.L., Greenberg, S.A., Trojanowski, J.Q., Traynor, B.J., Smith, B.N., Topp, S., Gkazi, A.S., Miller, J., Shaw, C.E., Kottlors, M., Kirschner, J., Pestronk, A., Li, Y.R., Ford, A.F., Gitler, A.D., Benatar, M., King, O.D., Kimonis, V.E., Ross, E.D., Weihl, C.C., Shorter, J., Taylor, J.P., Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495 (2013), 467–473.
142. King, O.D., Gitler, A.D., Shorter, J., The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 1462 (2012), 61–80.
143. King, A., Troakes, C., Smith, B., Nolan, M., Curran, O., Vance, C., Shaw, C.E., Al-Sarraj, S., ALS-FUS pathology revisited: singleton FUS mutations and an unusual case with both a FUS and TARDBP mutation. Acta Neuropathol. Commun., 3, 2015, 62.
144. Kino, Y., Washizu, C., Aquilanti, E., Okuno, M., Kurosawa, M., Yamada, M., Doi, H., Nukina, N., Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations. Nucl. Acids Res. 39 (2011), 2781–2798.
145. Kovacs, G.G., Murrell, J.R., Horvath, S., Haraszti, L., Majtenyi, K., Molnar, M.J., Budka, H., Ghetti, B., Spina, S., TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov. Disord. 24 (2009), 1843–1847.
146. Kraemer, B.C., Schuck, T., Wheeler, J.M., Robinson, L.C., Trojanowski, J.Q., Lee, V.M., Schellenberg, G.D., Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis. Acta Neuropathol. 119 (2010), 409–419.
147. Kuo, P.H., Doudeva, L.G., Wang, Y.T., Shen, C.K., Yuan, H.S., Structural insights into TDP-43 in nucleic-acid binding and domain interactions. Nucl. Acids Res. 37 (2009), 1799–1808.
148. Kuo, P.H., Chiang, C.H., Wang, Y.T., Doudeva, L.G., Yuan, H.S., The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids. Nucl. Acids Res. 42 (2014), 4712–4722.
149. Kuroda, M., Sok, J., Webb, L., Baechtold, H., Urano, F., Yin, Y., Chung, P., de Rooij, D.G., Akhmedov, A., Ashley, T., Ron, D., Male sterility and enhanced radiation sensitivity in TLS(-/-) mice. EMBO J. 19 (2000), 453–462.
150. 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 323 (2009), 1205–1208.
151. Kwong, L.K., Neumann, M., Sampathu, D.M., Lee, V.M., Trojanowski, J.Q., TDP-43 proteinopathy: the neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol. 114 (2007), 63–70.
152. Lagier-Tourenne, C., Cleveland, D.W., Rethinking ALS: the FUS about TDP-43. Cell 136 (2009), 1001–1004.
153. Lanson, N.A. Jr., Pandey, U.B., FUS-related proteinopathies: lessons from animal models. Brain Res. 1462 (2012), 44–60.
154. Lanson, N.A. Jr., Maltare, A., King, H., Smith, R., Kim, J.H., Taylor, J.P., Lloyd, T.E., Pandey, U.B., A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43. Hum. Mol. Genet. 20 (2011), 2510–2523.
155. Leblond, C.S., Kaneb, H.M., Dion, P.A., Rouleau, G.A., Dissection of genetic factors associated with amyotrophic lateral sclerosis. Exp. Neurol. 262:Pt B (2014), 91–101.
156. Lee, B.J., Cansizoglu, A.E., Suel, K.E., Louis, T.H., Zhang, Z., Chook, Y.M., Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell 126 (2006), 543–558.
157. Lejeune, F., Maquat, L.E., Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr. Opin. Cell Biol. 17 (2005), 309–315.
158. Li, X., Decker, M., Westendorf, J.J., TEThered to Runx: novel binding partners for runx factors. Blood Cells Mol. Dis. 45 (2010), 82–85.
159. Li, Y.R., King, O.D., Shorter, J., Gitler, A.D., Stress granules as crucibles of ALS pathogenesis. J. Cell Biol. 201 (2013), 361–372.
160. Li, Q., Yokoshi, M., Okada, H., Kawahara, Y., The cleavage pattern of TDP-43 determines its rate of clearance and cytotoxicity. Nat. Commun., 6, 2015, 6183.
161. Liachko, N.F., Guthrie, C.R., Kraemer, B.C., Phosphorylation promotes neurotoxicity in a Caenorhabditis elegans model of TDP-43 proteinopathy. J. Neurosci. 30 (2010), 16208–16219.
162. Liachko, N.F., McMillan, P.J., Guthrie, C.R., Bird, T.D., Leverenz, J.B., Kraemer, B.C., CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration. Ann. Neurol. 74 (2013), 39–52.
163. Liachko, N.F., McMillan, P.J., Strovas, T.J., Loomis, E., Greenup, L., Murrell, J.R., Ghetti, B., Raskind, M.A., Montine, T.J., Bird, T.D., Leverenz, J.B., Kraemer, B.C., The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43. PLoS Genet., 10, 2014, e1004803.
164. Ling, S.C., Albuquerque, C.P., Han, J.S., Lagier-Tourenne, C., Tokunaga, S., Zhou, H., Cleveland, D.W., ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 13318–13323.
165. Ling, S.C., Polymenidou, M., Cleveland, D.W., Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 79 (2013), 416–438.
166. Lipton, A.M., White, C.L. 3rd, Bigio, E.H., Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration. Acta Neuropathol. 108 (2004), 379–385.
167. Liu, X., Li, D., Zhang, W., Guo, M., Zhan, Q., Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay. EMBO j. 31 (2012), 4415–4427.
168. Liu, R., Yang, G., Nonaka, T., Arai, T., Jia, W., Cynader, M.S., Reducing TDP-43 aggregation does not prevent its cytotoxicity. Acta Neuropathol. Commun, 1, 2013, 49.
169. LoGerfo, A., Chico, L., Borgia, L., Petrozzi, L., Rocchi, A., D'Amelio, A., Carlesi, C., Caldarazzo Ienco, E., Mancuso, M., Siciliano, G., Lack of association between nuclear factor erythroid-derived 2-like 2 promoter gene polymorphisms and oxidative stress biomarkers in amyotrophic lateral sclerosis patients. Oxid. Med. Cell. Longev., 2014, 2014, 432626.
170. Mackenzie, I.R., Munoz, D.G., Kusaka, H., Yokota, O., Ishihara, K., Roeber, S., Kretzschmar, H.A., Cairns, N.J., Neumann, M., Distinct pathological subtypes of FTLD-FUS. Acta Neuropathol. 121 (2011), 207–218.
171. Madabhushi, R., Gao, F., Pfenning, A.R., Pan, L., Yamakawa, S., Seo, J., Rueda, R., Phan, T.X., Yamakawa, H., Pao, P.C., Stott, R.T., Gjoneska, E., Nott, A., Cho, S., Kellis, M., Tsai, L.H., Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 161 (2015), 1592–1605.
172. Maekawa, S., Leigh, P.N., King, A., Jones, E., Steele, J.C., Bodi, I., Shaw, C.E., Hortobagyi, T., Al-Sarraj, S., TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations. Neuropathology 29 (2009), 672–683.
173. Mantovani, S., Garbelli, S., Pasini, A., Alimonti, D., Perotti, C., Melazzini, M., Bendotti, C., Mora, G., Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process. J. Neuroimmunol. 210 (2009), 73–79.
174. Martin, L.J., Chen, K., Liu, Z., Adult motor neuron apoptosis is mediated by nitric oxide and Fas death receptor linked by DNA damage and p53 activation. J. Neurosci. 25 (2005), 6449–6459.
175. Martin, L.J., Liu, Z., Chen, K., Price, A.C., Pan, Y., Swaby, J.A., Golden, W.C., Motor neuron degeneration in amyotrophic lateral sclerosis mutant superoxide dismutase-1 transgenic mice: mechanisms of mitochondriopathy and cell death. J. Comp. Neurol. 500 (2007), 20–46.
176. Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., Komure, O., Matsuura, S., Kobatake, K., Morimoto, N., Abe, K., Suzuki, N., Aoki, M., Kawata, A., Hirai, T., Kato, T., Ogasawara, K., Hirano, A., Takumi, T., Kusaka, H., Hagiwara, K., Kaji, R., Kawakami, H., Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465 (2010), 223–226.
177. Mastrocola, A.S., Kim, S.H., Trinh, A.T., Rodenkirch, L.A., Tibbetts, R.S., The RNA-binding protein fused in sarcoma (FUS) functions downstream of poly(ADP-ribose) polymerase (PARP) in response to DNA damage. J. Biol. Chem. 288 (2013), 24731–24741.
178. McCluskey, L.F., Elman, L.B., Martinez-Lage, M., Van Deerlin, V., Yuan, W., Clay, D., Siderowf, A., Trojanowski, J.Q., Amyotrophic lateral sclerosis-plus syndrome with TAR DNA-binding protein-43 pathology. Arch. Neurol. 66 (2009), 121–124.
179. McDonald, K.K., Aulas, A., Destroismaisons, L., Pickles, S., Beleac, E., Camu, W., Rouleau, G.A., Vande Velde, C., TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Hum. Mol. Genet. 20 (2011), 1400–1410.
180. McGurk, L., Lee, V.M., Trojanowksi, J.Q., Van Deerlin, V.M., Lee, E.B., Bonini, N.M., Poly-A binding protein-1 localization to a subset of TDP-43 inclusions in amyotrophic lateral sclerosis occurs more frequently in patients harboring an expansion in C9orf72. J. Neuropathol. Exp. Neurol. 73 (2014), 837–845.
181. Mitra, J., Guerrero, E.N., Hegde, P.M., Wang, H., Boldogh, I., Rao, K.S., Mitra, S., Hegde, M.L., New perspectives on oxidized genome damage and repair inhibition by pro-oxidant metals in neurological diseases. Biomolecules 4 (2014), 678–703.
182. Mitra, J., Vasquez, V., Hegde, P.M., Boldogh, I., Mitra, S., Kent, T.A., Rao, K.S., Hegde, M.L., Revisiting metal toxicity in neurodegenerative diseases and stroke: therapeutic potential. Neurol. Res. Ther., 1, 2014.
183. Mitsuyama, Y., Presenile dementia with motor neuron disease. Dementia 4 (1993), 137–142.
184. Mladinic, M., Lefevre, C., Del Bel, E., Nicholls, J., Digby, M., Developmental changes of gene expression after spinal cord injury in neonatal opossums. Brain Res. 1363 (2010), 20–39.
185. Morohoshi, F., Ootsuka, Y., Arai, K., Ichikawa, H., Mitani, S., Munakata, N., Ohki, M., Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes. Gene 221 (1998), 191–198.
186. Nagase, M., Yamamoto, Y., Miyazaki, Y., Yoshino, H., Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration. Redox Rep. 21 (2016), 104–112.
187. Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S.X., Hurtig, H., Duda, J.E., Arnold, S.E., Siderowf, A., Grossman, M., Leverenz, J.B., Woltjer, R., Lopez, O.L., Hamilton, R., Tsuang, D.W., Galasko, D., Masliah, E., Kaye, J., Clark, C.M., Montine, T.J., Lee, V.M., Trojanowski, J.Q., Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol. 114 (2007), 221–229.
188. Neumann, M., Sampathu, D.M., Kwong, L.K., Truax, A.C., Micsenyi, M.C., Chou, T.T., Bruce, J., Schuck, T., Grossman, M., Clark, C.M., McCluskey, L.F., Miller, B.L., Masliah, E., Mackenzie, I.R., Feldman, H., Feiden, W., Kretzschmar, H.A., Trojanowski, J.Q., Lee, V.M., Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314 (2006), 130–133.
189. Neumann, M., Kwong, L.K., Lee, E.B., Kremmer, E., Flatley, A., Xu, Y., Forman, M.S., Troost, D., Kretzschmar, H.A., Trojanowski, J.Q., Lee, V.M., Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol. 117 (2009), 137–149.
190. Niedzielska, E., Smaga, I., Gawlik, M., Moniczewski, A., Stankowicz, P., Pera, J., Filip, M., Oxidative stress in neurodegenerative diseases. Mol. Neurobiol. 53 (2016), 4094–4125.
191. Niu, C., Zhang, J., Gao, F., Yang, L., Jia, M., Zhu, H., Gong, W., FUS-NLS/transportin 1 complex structure provides insights into the nuclear targeting mechanism of FUS and the implications in ALS. PLoS One, 7, 2012, e47056.
192. Nomura, T., Watanabe, S., Kaneko, K., Yamanaka, K., Nukina, N., Furukawa, Y., Intranuclear aggregation of mutant FUS/TLS as a molecular pathomechanism of amyotrophic lateral sclerosis. J. Biol. Chem. 289 (2014), 1192–1202.
193. Nonaka, T., Suzuki, G., Tanaka, Y., Kametani, F., Hirai, S., Okado, H., Miyashita, T., Saitoe, M., Akiyama, H., Masai, H., Hasegawa, M., Phosphorylation of TAR DNA-binding protein of 43 kDa (TDP-43) by truncated casein kinase 1delta triggers mislocalization and accumulation of TDP-43. J. Biol. Chem. 291 (2016), 5473–5483.
194. Osawa, T., Mizuno, Y., Fujita, Y., Takatama, M., Nakazato, Y., Okamoto, K., Optineurin in neurodegenerative diseases. Neuropathology 31 (2011), 569–574.
195. Ou, S.H., Wu, F., Harrich, D., Garcia-Martinez, L.F., Gaynor, R.B., Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J. Virol. 69 (1995), 3584–3596.
196. Panagopoulos, I., Aman, P., Fioretos, T., Hoglund, M., Johansson, B., Mandahl, N., Heim, S., Behrendtz, M., Mitelman, F., Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosomes Cancer 11 (1994), 256–262.
197. Pasinelli, P., Brown, R.H., Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci. 7 (2006), 710–723.
198. Pedersen, W.A., Fu, W., Keller, J.N., Markesbery, W.R., Appel, S., Smith, R.G., Kasarskis, E., Mattson, M.P., Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann. Neurol. 44 (1998), 819–824.
199. Perl, D.P., Gajdusek, D.C., Garruto, R.M., Yanagihara, R.T., Gibbs, C.J., Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Science 217 (1982), 1053–1055.
200. Philips, T., Robberecht, W., Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10 (2011), 253–263.
201. Plato, C.C., Garruto, R.M., Galasko, D., Craig, U.K., Plato, M., Gamst, A., Torres, J.M., Wiederholt, W., Amyotrophic lateral sclerosis and parkinsonism-dementia complex of Guam: changing incidence rates during the past 60 years. Am. J. Epidemiol. 157 (2003), 149–157.
202. Polymenidou, M., Lagier-Tourenne, C., Hutt, K.R., Huelga, S.C., Moran, J., Liang, T.Y., Ling, S.C., Sun, E., Wancewicz, E., Mazur, C., Kordasiewicz, H., Sedaghat, Y., Donohue, J.P., Shiue, L., Bennett, C.F., Yeo, G.W., Cleveland, D.W., Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat. Neurosci. 14 (2011), 459–468.
203. Powers, C.A., Mathur, M., Raaka, B.M., Ron, D., Samuels, H.H., TLS (translocated-in-liposarcoma) is a high-affinity interactor for steroid, thyroid hormone, and retinoid receptors. Mol. Endocrinol. 12 (1998), 4–18.
204. Prasad, D.D., Ouchida, M., Lee, L., Rao, V.N., Reddy, E.S., TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain. Oncogene 9 (1994), 3717–3729.
205. Qiu, H., Lee, S., Shang, Y., Wang, W.Y., Au, K.F., Kamiya, S., Barmada, S.J., Finkbeiner, S., Lui, H., Carlton, C.E., Tang, A.A., Oldham, M.C., Wang, H., Shorter, J., Filiano, A.J., Roberson, E.D., Tourtellotte, W.G., Chen, B., Tsai, L.H., Huang, E.J., ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects. J. Clin. Invest. 124 (2014), 981–999.
206. Rabbitts, T.H., Forster, A., Larson, R., Nathan, P., Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat. Genet. 4 (1993), 175–180.
207. Rao, S.D., Banack, S.A., Cox, P.A., Weiss, J.H., BMAA selectively injures motor neurons via AMPA/kainate receptor activation. Exp. Neurol. 201 (2006), 244–252.
208. Rappsilber, J., Friesen, W.J., Paushkin, S., Dreyfuss, G., Mann, M., Detection of arginine dimethylated peptides by parallel precursor ion scanning mass spectrometry in positive ion mode. Anal. Chem. 75 (2003), 3107–3114.
209. Ravits, J., Appel, S., Baloh, R.H., Barohn, R., Brooks, B.R., Elman, L., Floeter, M.K., Henderson, C., Lomen-Hoerth, C., Macklis, J.D., McCluskey, L., Mitsumoto, H., Przedborski, S., Rothstein, J., Trojanowski, J.Q., van den Berg, L.H., Ringel, S., Deciphering amyotrophic lateral sclerosis: what phenotype, neuropathology and genetics are telling us about pathogenesis. Amyotroph. Lateral Scler. Frontotemporal. Degener. 14:Suppl. 1 (2013), 5–18.
210. Robinson, H.K., Deykin, A.V., Bronovitsky, E.V., Ovchinnikov, R.K., Ustyugov, A.A., Shelkovnikova, T.A., Kukharsky, M.S., Ermolkevich, T.G., Goldman, I.L., Sadchikova, E.R., Kovrazhkina, E.A., Bachurin, S.O., Buchman, V.L., Ninkina, N.N., Early lethality and neuronal proteinopathy in mice expressing cytoplasm-targeted FUS that lacks the RNA recognition motif. Amyotroph. Lateral Scler. Frontotemporal Degener. 16 (2015), 402–409.
211. Ron, D., Walter, P., Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell. Biol. 8 (2007), 519–529.
212. Rosen, D.R., Siddique, T., Patterson, D., Figlewicz, D.A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J.P., Deng, H.X., et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362 (1993), 59–62.
213. Rulten, S.L., Rotheray, A., Green, R.L., Grundy, G.J., Moore, D.A., Gomez-Herreros, F., Hafezparast, M., Caldecott, K.W., PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS/TLS to sites of oxidative DNA damage. Nucl. Acids Res. 42 (2014), 307–314.
214. Rutherford, N.J., Zhang, Y.J., Baker, M., Gass, J.M., Finch, N.A., Xu, Y.F., Stewart, H., Kelley, B.J., Kuntz, K., Crook, R.J., Sreedharan, J., Vance, C., Sorenson, E., Lippa, C., Bigio, E.H., Geschwind, D.H., Knopman, D.S., Mitsumoto, H., Petersen, R.C., Cashman, N.R., Hutton, M., Shaw, C.E., Boylan, K.B., Boeve, B., Graff-Radford, N.R., Wszolek, Z.K., Caselli, R.J., Dickson, D.W., Mackenzie, I.R., Petrucelli, L., Rademakers, R., Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet., 4, 2008, e1000193.
215. Saccon, R.A., Bunton-Stasyshyn, R.K., Fisher, E.M., Fratta, P., Is SOD1 loss of function involved in amyotrophic lateral sclerosis?. Brain 136 (2013), 2342–2358.
216. Salajegheh, M., Pinkus, J.L., Taylor, J.P., Amato, A.A., Nazareno, R., Baloh, R.H., Greenberg, S.A., Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis. Muscle Nerve 40 (2009), 19–31.
217. Salih, D.A., Brunet, A., FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr. Opin. Cell. Biol. 20 (2008), 126–136.
218. Salvi, J.S., Mekhail, K., R-loops highlight the nucleus in ALS. Nucleus 6 (2015), 23–29.
219. Sama, R.R., 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. 228 (2013), 2222–2231.
220. Sama, R.R., Ward, C.L., Bosco, D.A., Functions of FUS/TLS from DNA repair to stress response: implications for ALS. ASN Neuro, 6, 2014.
221. Sasaki, S., Iguchi, Y., Katsuno, M., Sobue, G., Alterations in the blood-spinal cord barrier in TDP-43 conditional knockout mice. Neurosci. Lett. 598 (2015), 1–5.
222. Scaramuzzino, C., Monaghan, J., Milioto, C., Lanson, N.A. Jr., Maltare, A., Aggarwal, T., Casci, I., Fackelmayer, F.O., Pennuto, M., Pandey, U.B., Protein arginine methyltransferase 1 and 8 interact with FUS to modify its sub-cellular distribution and toxicity in vitro and in vivo. PLoS One, 8, 2013, e61576.
223. Schmidt, S., Kwee, L.C., Allen, K.D., Oddone, E.Z., Association of ALS with head injury, cigarette smoking and APOE genotypes. J. Neurol. Sci. 291 (2010), 22–29.
224. Schmitz, K.M., Schmitt, N., Hoffmann-Rohrer, U., Schafer, A., Grummt, I., Mayer, C., TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol. Cell 33 (2009), 344–353.
225. Scotter, E.L., Vance, C., Nishimura, A.L., Lee, Y.B., Chen, H.J., Urwin, H., Sardone, V., Mitchell, J.C., Rogelj, B., Rubinsztein, D.C., Shaw, C.E., Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species. J. Cell Sci. 127 (2014), 1263–1278.
226. Sephton, C.F., Yu, G., The function of RNA-binding proteins at the synapse: implications for neurodegeneration. Cell. Mol. Life Sci. 72 (2015), 3621–3635.
227. Sephton, C.F., Good, S.K., Atkin, S., Dewey, C.M., Mayer, P. 3rd, Herz, J., Yu, G., TDP-43 is a developmentally regulated protein essential for early embryonic development. J. Biol. Chem. 285 (2010), 6826–6834.
228. 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. 286 (2011), 1204–1215.
229. Shaikh, A.Y., Martin, L.J., DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis. Neuromol. Med. 2 (2002), 47–60.
230. Shan, X., Chiang, P.M., Price, D.L., Wong, P.C., Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 16325–16330.
231. Sharma, A., Lyashchenko, A.K., Lu, L., Nasrabady, S.E., Elmaleh, M., Mendelsohn, M., Nemes, A., Tapia, J.C., Mentis, G.Z., Shneider, N.A., ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function. Nat. Commun., 7, 2016, 10465.
232. 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. 288 (2013), 25266–25274.
233. Shelkovnikova, T.A., Robinson, H.K., Connor-Robson, N., Buchman, V.L., Recruitment into stress granules prevents irreversible aggregation of FUS protein mislocalized to the cytoplasm. Cell Cycle 12 (2013), 3194–3202.
234. Shiina, Y., Arima, K., Tabunoki, H., Satoh, J., TDP-43 dimerizes in human cells in culture. Cell. Mol. Neurobiol. 30 (2010), 641–652.
235. Shing, D.C., McMullan, D.J., Roberts, P., Smith, K., Chin, S.F., Nicholson, J., Tillman, R.M., Ramani, P., Cullinane, C., Coleman, N., FUS/ERG gene fusions in Ewing's tumors. Cancer Res. 63 (2003), 4568–4576.
236. Shiwaku, H., Okazawa, H., Impaired DNA damage repair as a common feature of neurodegenerative diseases and psychiatric disorders. Curr. Mol. Med. 15 (2015), 119–128.
237. 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.
238. 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 319 (2008), 1668–1672.
239. Stallings, N.R., Puttaparthi, K., Luther, C.M., Burns, D.K., Elliott, J.L., Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol. Dis. 40 (2010), 404–414.
240. Suberbielle, E., Sanchez, P.E., Kravitz, A.V., Wang, X., Ho, K., Eilertson, K., Devidze, N., Kreitzer, A.C., Mucke, L., Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-beta. Nat. Neurosci. 16 (2013), 613–621.
241. Swarup, V., Phaneuf, D., Bareil, C., Robertson, J., Rouleau, G.A., Kriz, J., Julien, J.P., Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain 134 (2011), 2610–2626.
242. Swarup, V., Phaneuf, D., Dupre, N., Petri, S., Strong, M., Kriz, J., Julien, J.P., Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. J. Exp. Med. 208 (2011), 2429–2447.
243. Tan, A.Y., Manley, J.L., The TET family of proteins: functions and roles in disease. J. Mol. Cell Biol. 1 (2009), 82–92.
244. Tan, A.Y., Manley, J.L., TLS inhibits RNA polymerase III transcription. Mol. Cell. Biol. 30 (2010), 186–196.
245. Tan, C.F., Eguchi, H., Tagawa, A., Onodera, O., Iwasaki, T., Tsujino, A., Nishizawa, M., Kakita, A., Takahashi, H., TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation. Acta Neuropathol. 113 (2007), 535–542.
246. Thorpe, J.R., Tang, H., Atherton, J., Cairns, N.J., Fine structural analysis of the neuronal inclusions of frontotemporal lobar degeneration with TDP-43 proteinopathy. J. Neural Transm. 115 (2008), 1661–1671.
247. Tibshirani, M., Tradewell, M.L., Mattina, K.R., Minotti, S., Yang, W., Zhou, H., Strong, M.J., Hayward, L.J., Durham, H.D., Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1. Hum. Mol. Genet. 24 (2015), 773–786.
248. Ticozzi, N., Silani, V., LeClerc, A.L., Keagle, P., Gellera, C., Ratti, A., Taroni, F., Kwiatkowski, T.J. Jr., McKenna-Yasek, D.M., Sapp, P.C., Brown, R.H. Jr., Landers, J.E., Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis within an Italian cohort. Neurology 73 (2009), 1180–1185.
249. Tolino, M., Kohrmann, M., Kiebler, M.A., RNA-binding proteins involved in RNA localization and their implications in neuronal diseases. Eur. J. Neurosci. 35 (2012), 1818–1836.
250. Tollervey, J.R., Curk, T., Rogelj, B., Briese, M., Cereda, M., Kayikci, M., Konig, J., Hortobagyi, T., Nishimura, A.L., Zupunski, V., Patani, R., Chandran, S., Rot, G., Zupan, B., Shaw, C.E., Ule, J., Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat. Neurosci. 14 (2011), 452–458.
251. Tourriere, H., Chebli, K., Zekri, L., Courselaud, B., Blanchard, J.M., Bertrand, E., Tazi, J., The RasGAP-associated endoribonuclease G3BP assembles stress granules. J. Cell Biol. 160 (2003), 823–831.
252. Tradewell, M.L., Yu, Z., Tibshirani, M., Boulanger, M.C., Durham, H.D., Richard, S., Arginine methylation by PRMT1 regulates nuclear-cytoplasmic localization and toxicity of FUS/TLS harbouring ALS-linked mutations. Hum. Mol. Genet. 21 (2012), 136–149.
253. Tsai, K.J., Yang, C.H., Fang, Y.H., Cho, K.H., Chien, W.L., Wang, W.T., Wu, T.W., Lin, C.P., Fu, W.M., Shen, C.K., Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. J. Exp. Med. 207 (2010), 1661–1673.
254. Turner, M.R., Cagnin, A., Turkheimer, F.E., Miller, C.C., Shaw, C.E., Brooks, D.J., Leigh, P.N., Banati, R.B., Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol. Dis. 15 (2004), 601–609.
255. Uranishi, H., Tetsuka, T., Yamashita, M., Asamitsu, K., Shimizu, M., Itoh, M., Okamoto, T., Involvement of the pro-oncoprotein TLS (translocated in liposarcoma) in nuclear factor-kappa B p65-mediated transcription as a coactivator. J. Biol. Chem. 276 (2001), 13395–13401.
256. van Blitterswijk, M., Wang, E.T., Friedman, B.A., Keagle, P.J., Lowe, P., Leclerc, A.L., van den Berg, L.H., Housman, D.E., Veldink, J.H., Landers, J.E., Characterization of FUS mutations in amyotrophic lateral sclerosis using RNA-Seq. PLoS One, 8, 2013, e60788.
257. van Eersel, J., Ke, Y.D., Gladbach, A., Bi, M., Gotz, J., Kril, J.J., Ittner, L.M., Cytoplasmic accumulation and aggregation of TDP-43 upon proteasome inhibition in cultured neurons. PLoS One, 6, 2011, e22850.
258. Valdmanis, P.N., Daoud, H., Dion, P.A., Rouleau, G.A., Recent advances in the genetics of amyotrophic lateral sclerosis. Curr. Neurol. Neurosci. Rep. 9 (2009), 198–205.
259. 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. 7 (2008), 409–416.
260. 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 323 (2009), 1208–1211.
261. 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.
262. Waibel, S., Neumann, M., Rosenbohm, A., Birve, A., Volk, A.E., Weishaupt, J.H., Meyer, T., Muller, U., Andersen, P.M., Ludolph, A.C., Truncating mutations in FUS/TLS give rise to a more aggressive ALS-phenotype than missense mutations: a clinico-genetic study in Germany. Eur. J. Neurol. 20 (2013), 540–546.
263. Walker, A.K., Daniels, C.M., Goldman, J.E., Trojanowski, J.Q., Lee, V.M., Messing, A., Astrocytic TDP-43 pathology in Alexander disease. J. Neurosci. 34 (2014), 6448–6458.
264. Walker, A.K., Spiller, K.J., Ge, G., Zheng, A., Xu, Y., Zhou, M., Tripathy, K., Kwong, L.K., Trojanowski, J.Q., Lee, V.M., Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43. Acta Neuropathol. 130 (2015), 643–660.
265. Wang, H.Y., Wang, I.F., Bose, J., Shen, C.K., Structural diversity and functional implications of the eukaryotic TDP gene family. Genomics 83 (2004), 130–139.
266. Wang, I.F., Wu, L.S., Chang, H.Y., Shen, C.K., TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. J. Neurochem. 105 (2008), 797–806.
267. Wang, J.W., Brent, J.R., Tomlinson, A., Shneider, N.A., McCabe, B.D., The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span. J. Clin. Invest. 121 (2011), 4118–4126.
268. Wang, W., Li, L., Lin, W.L., Dickson, D.W., Petrucelli, L., Zhang, T., Wang, X., The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons. Hum. Mol. Genet. 22 (2013), 4706–4719.
269. Wang, W.Y., Pan, L., Su, S.C., Quinn, E.J., Sasaki, M., Jimenez, J.C., Mackenzie, I.R., Huang, E.J., Tsai, L.H., Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons. Nat. Neurosci. 16 (2013), 1383–1391.
270. Wang, H., Adhikari, S., Butler, B.E., Pandita, T.K., Mitra, S., Hegde, M.L., A perspective on chromosomal double strand break markers in mammalian cells. Jacobs J. Radiat. Oncol., 2014, 1.
271. Watts, G.D., Wymer, J., Kovach, M.J., Mehta, S.G., Mumm, S., Darvish, D., Pestronk, A., Whyte, M.P., Kimonis, V.E., Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat. Genet. 36 (2004), 377–381.
272. Wegorzewska, I., Bell, S., Cairns, N.J., Miller, T.M., Baloh, R.H., TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 18809–18814.
273. Weiss, J.H., Koh, J.Y., Choi, D.W., Neurotoxicity of beta-N-methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) on cultured cortical neurons. Brain Res. 497 (1989), 64–71.
274. Weisskopf, M.G., Morozova, N., O'Reilly, E.J., McCullough, M.L., Calle, E.E., Thun, M.J., Ascherio, A., Prospective study of chemical exposures and amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 80 (2009), 558–561.
275. Williams, K.L., Warraich, S.T., Yang, S., Solski, J.A., Fernando, R., Rouleau, G.A., Nicholson, G.A., Blair, I.P., UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis. Neurobiol. Aging 33:2527 (2012), e2510–e2523.
276. 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. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 3858–3863.
277. Wu, L.S., Cheng, W.C., Hou, S.C., Yan, Y.T., Jiang, S.T., Shen, C.K., TDP-43, a neuro-pathosignature factor, is essential for early mouse embryogenesis. Genesis 48 (2010), 56–62.
278. 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. 287 (2012), 27335–27344.
279. Xiao, S., Sanelli, T., Dib, S., Sheps, D., Findlater, J., Bilbao, J., Keith, J., Zinman, L., Rogaeva, E., Robertson, J., RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS. Mol. Cell Neurosci. 47 (2011), 167–180.
280. Xiao, S., Sanelli, T., Chiang, H., Sun, Y., Chakrabartty, A., Keith, J., Rogaeva, E., Zinman, L., Robertson, J., Low molecular weight species of TDP-43 generated by abnormal splicing form inclusions in amyotrophic lateral sclerosis and result in motor neuron death. Acta Neuropathol. 130 (2015), 49–61.
281. Xu, Y.F., Gendron, T.F., Zhang, Y.J., Lin, W.L., D'Alton, S., Sheng, H., Casey, M.C., Tong, J., Knight, J., Yu, X., Rademakers, R., Boylan, K., Hutton, M., McGowan, E., Dickson, D.W., Lewis, J., Petrucelli, L., Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J. Neurosci. 30 (2010), 10851–10859.
282. Xu, Y.F., Zhang, Y.J., Lin, W.L., Cao, X., Stetler, C., Dickson, D.W., Lewis, J., Petrucelli, L., Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice. Mol. Neurodegener., 6, 2011, 73.
283. Yan, J., Deng, H.X., Siddique, N., Fecto, F., Chen, W., Yang, Y., Liu, E., Donkervoort, S., Zheng, J.G., Shi, Y., Ahmeti, K.B., Brooks, B., Engel, W.K., Siddique, T., Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia. Neurology 75 (2010), 807–814.
284. Yanagihara, R., Garruto, R.M., Gajdusek, D.C., Tomita, A., Uchikawa, T., Konagaya, Y., Chen, K.M., Sobue, I., Plato, C.C., Gibbs, C.J. Jr., Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia. Ann. Neurol. 15 (1984), 42–48.
285. Yang, C., Tan, W., Whittle, C., Qiu, L., Cao, L., Akbarian, S., Xu, Z., The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PLoS One, 5, 2010, e15878.
286. Yang, C., Wang, H., Qiao, T., Yang, B., Aliaga, L., Qiu, L., Tan, W., Salameh, J., McKenna-Yasek, D.M., Smith, T., Peng, L., Moore, M.J., Brown, R.H. Jr., Cai, H., Xu, Z., Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), E1121–1129.
287. Yasui, M., Ota, K., Garruto, R.M., Concentrations of zinc and iron in the brains of Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia. Neurotoxicology 14 (1993), 445–450.
288. Zhang, Y.J., Xu, Y.F., Dickey, C.A., Buratti, E., Baralle, F., Bailey, R., Pickering-Brown, S., Dickson, D., Petrucelli, L., Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J. Neurosci. 27 (2007), 10530–10534.
289. Zhang, Y.J., Xu, Y.F., Cook, C., Gendron, T.F., Roettges, P., Link, C.D., Lin, W.L., Tong, J., Castanedes-Casey, M., Ash, P., Gass, J., Rangachari, V., Buratti, E., Baralle, F., Golde, T.E., Dickson, D.W., Petrucelli, L., Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 7607–7612.
290. Zhang, Y.J., Gendron, T.F., Xu, Y.F., Ko, L.W., Yen, S.H., Petrucelli, L., Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments. Mol. Neurodegener., 5, 2010, 33.
291. Zhang, T., Baldie, G., Periz, G., Wang, J., RNA-processing protein TDP-43 regulates FOXO-dependent protein quality control in stress response. PLoS Genet., 10, 2014, e1004693.
292. Zhang, K., Donnelly, C.J., Haeusler, A.R., Grima, J.C., Machamer, J.B., Steinwald, P., Daley, E.L., Miller, S.J., Cunningham, K.M., Vidensky, S., Gupta, S., Thomas, M.A., Hong, I., Chiu, S.L., Huganir, R.L., Ostrow, L.W., Matunis, M.J., Wang, J., Sattler, R., Lloyd, T.E., Rothstein, J.D., The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525 (2015), 56–61.
293. Zhou, H., Huang, C., Chen, H., Wang, D., Landel, C.P., Xia, P.Y., Bowser, R., Liu, Y.J., Xia, X.G., Transgenic rat model of neurodegeneration caused by mutation in the TDP gene. PLoS Genet., 6, 2010, e1000887.
294. Zhou, Y., Liu, S., Liu, G., Ozturk, A., Hicks, G.G., ALS-associated FUS mutations result in compromised FUS alternative splicing and autoregulation. PLoS Genet., 9, 2013, e1003895.
295. Zinszner, H., Albalat, R., Ron, D., A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes Dev. 8 (1994), 2513–2526.