TDP-43-based animal models of neurodegeneration: New insights into ALS pathology and pathophysiology

Neurodegenerative Diseases

Volumn 8, Issue 4, 2011, Pages 262-274

  Wegorzewska, Iga ^a   Baloh, Robert H ^a,b,c  

^a Neuromuscular Division   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Box 8111 ^*  (United States)

Author keywords

Amyotrophic lateral sclerosis; Frontotemporal lobar degeneration; Motor neuron disease; Protein aggregation; TDP 43

Indexed keywords

DNA BINDING PROTEIN; RNA BINDING PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL NUCLEUS; CLINICAL FEATURE; CONTROLLED STUDY; CYTOPLASM; DEGENERATIVE DISEASE; DISEASE ASSOCIATION; FRONTOTEMPORAL DEMENTIA; GENE MUTATION; GENE OVEREXPRESSION; HOMEOSTASIS; MOTOR NEURON DISEASE; NEUROPATHOLOGY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN FUNCTION; TDP 43 PROTEINOPATHY;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; FRONTOTEMPORAL LOBAR DEGENERATION; HUMANS; NERVE DEGENERATION;

EID: 79955812764     PISSN: 16602854     EISSN: 16602862     Source Type: Journal    
DOI: 10.1159/000321547     Document Type: Article

References (88)

1. Bruijn LI, Miller TM, Cleveland DW: Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 2004; 27: 723-749. (Pubitemid 39050419)
2. Siddique T, Lalani I: Genetic aspects of amyotrophic lateral sclerosis. Adv Neurol 2002; 88: 21-32.
3. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, et al: Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59-62. (Pubitemid 23087289)
4. Benatar M: Lost in translation: treatment trials in the SOD1 mouse and in human ALS. Neurobiol Dis 2007; 26: 1-13. (Pubitemid 46437445)
5. Murphy J, Henry R, Lomen-Hoerth C: Establishing subtypes of the continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007; 64: 330-334. (Pubitemid 46425686)
6. Seeley WW: Selective functional, regional, and neuronal vulnerability in frontotemporal dementia. Curr Opin Neurol 2008; 21: 701-707.
7. Geser F, Martinez-Lage M, Robinson J, Uryu K, Neumann M, Brandmeir NJ, Xie SX, Kwong LK, Elman L, McCluskey L, Clark CM, Malunda J, Miller BL, Zimmerman EA, Qian J, Van Deerlin V, Grossman M, Lee VM, Trojanowski JQ: Clinical and pathological continuum of multisystem TDP-43 proteinopathies. Arch Neurol 2009; 66: 180-189.
8. Lomen-Hoerth C, Anderson T, Miller B: The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002; 59: 1077-1079.
9. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM: Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314: 130-133. (Pubitemid 44547757)
10. Acharya KK, Govind CK, Shore AN, Stoler MH, Reddi PP: cis-requirement for the maintenance of round spermatid-specific transcription. Dev Biol 2006; 295: 781-790. (Pubitemid 43927709)
11. Buratti E, Baralle FE: 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 2001; 276: 36337-36343.
12. Ayala YM, Pantano S, D'Ambrogio A, Buratti E, Brindisi A, Marchetti C, Romano M, Baralle FE: Human, Drosophila , and C. elegans TDP43: nucleic acid binding properties and splicing regulatory function. J Mol Biol 2005; 348: 575-588. (Pubitemid 40515670)
13. Buratti E, Baralle FE: The molecular links between TDP-43 dysfunction and neurodegeneration. Adv Genet 2009; 66: 1-34.
14. Gitcho MA, Baloh RH, Chakraverty S, Mayo K, Norton JB, Levitch D, Hatanpaa KJ, White CL 3rd, Bigio EH, Caselli R, Baker M, Al-Lozi MT, Morris JC, Pestronk A, Rademakers R, Goate AM, Cairns NJ: TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 2008; 63: 535-538. (Pubitemid 351614720)
15. Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA: TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 2008; 40: 572-574. (Pubitemid 351601218)
16. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE: TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319: 1668-1672. (Pubitemid 351432505)
17. Yokoseki A, Shiga A, Tan CF, Tagawa A, Kaneko H, Koyama A, Eguchi H, Tsujino A, Ikeuchi T, Kakita A, Okamoto K, Nishizawa M, Takahashi H, Onodera O: TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 2008; 63: 538-542. (Pubitemid 351614721)
18. Van Deerlin VM, Leverenz JB, Bekris LM, Bird TD, Yuan W, Elman LB, Clay D, Wood EM, Chen-Plotkin AS, Martinez-Lage M, Steinbart E, McCluskey L, Grossman M, Neumann M, Wu IL, Yang WS, Kalb R, Galasko DR, Montine TJ, Trojanowski JQ, Lee VM, Schellenberg GD, Yu CE: TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 2008; 7: 409-416.
19. 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: TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol 2009; 65: 470-473.
20. Gitcho MA, Bigio EH, Mishra M, Johnson N, Weintraub S, Mesulam M, Rademakers R, Chakraverty S, Cruchaga C, Morris JC, Goate AM, Cairns NJ: TARDBP 3 ′-UTR variant in autopsy-confirmed frontotemporal lobar degeneration with TDP-43 proteinopathy. Acta Neuropathol 2009; 118: 633-645.
21. Kovacs GG, Murrell JR, Horvath S, Haraszti L, Majtenyi K, Molnar MJ, Budka H, Ghetti B, Spina S: TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov Disord 2009; 24: 1843-1847.
22. 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 2009; 30:E974-E983.
23. Fuentealba RA, Udan M, Bell S, Wegorzewska I, Shao J, Diamond MI, Weihl CC, Baloh RH: Interaction with polyglutamine aggregates reveals a Q/N rich domain in TDP-43. J Biol Chem 2010; 285: 26304-26314.
24. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr: Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009; 323: 1205-1208.
25. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE: Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009; 323: 1208-1211.
26. Kim SH, Shanware N, Bowler MJ, Tibbetts RS: ALS-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to coregulate HDAC6 mRNA. J Biol Chem 2010; 285: 34097-34105.
27. Ling SC, Albuquerque CP, Han JS, Lagier-Tourenne C, Tokunaga S, Zhou H, Cleveland DW: ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci USA 2010; 107: 13318-13323.
28. Deng HX, Zhai H, Bigio EH, 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 2010; 67: 739-748.
29. Higashi S, Iseki E, Yamamoto R, Minegishi M, Hino H, Fujisawa K, Togo T, Katsuse O, Uchikado H, Furukawa Y, Kosaka K, Arai H: Concurrence of TDP-43, tau and alphasynuclein pathology in brains of Alzheimer's disease and dementia with Lewy bodies. Brain Res 2007; 1184: 284-294. (Pubitemid 350160566)
30. Josephs KA, Whitwell JL, Knopman DS, Hu WT, Stroh DA, Baker M, Rademakers R, Boeve BF, Parisi JE, Smith GE, Ivnik RJ, Petersen RC, Jack CR Jr, Dickson DW: Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 2008; 70: 1850-1857. (Pubitemid 351653955)
31. Schwab C, Arai T, Hasegawa M, Yu S, Mc-Geer PL: Colocalization of transactivationresponsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease. J Neuropathol Exp Neurol 2008; 67: 1159-1165.
32. Weihl CC, Temiz P, Miller SE, Watts G, Smith C, Forman M, Hanson PI, Kimonis V, Pestronk A: TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia. J Neurol Neurosurg Psychiatry 2008; 79: 1186-1189.
33. 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: 3785-3789. (Pubitemid 351723476)
34. Zhang YJ, Xu YF, Cook C, Gendron TF, Roettges P, Link CD, Lin WL, Tong J, Castanedes-Casey M, Ash P, Gass J, Rangachari V, Buratti E, Baralle F, Golde TE, Dickson DW, Petrucelli L: Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc Natl Acad Sci USA 2009; 106: 7607-7612.
35. Ash PE, Zhang YJ, Roberts CM, Saldi T, Hutter H, Buratti E, Petrucelli L, Link CD: Neurotoxic effects of TDP-43 overexpression in C. elegans . Hum Mol Genet 2010; 19: 3206-3218.
36. Gurney ME: Transgenic-mouse model of amyotrophic lateral sclerosis. N Engl J Med 1994; 331: 1721-1722. (Pubitemid 24373633)
37. Wegorzewska I, Bell S, Cairns NJ, Miller TM, Baloh RH: TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci USA 2009; 106: 18809-18814.
38. Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Groote CC, 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 USA 2010; 107: 3858-3863.
39. Stallings NR, Puttaparthi K, Luther CM, Burns DK, Elliott JL: Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol Dis 2010; 40: 404-414.
40. Tsai KJ, Yang CH, Fang YH, Cho KH, Chien WL, Wang WT, Wu TW, Lin CP, Fu WM, Shen CK: Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. J Exp Med 2010; 207: 1661-1673.
41. Xu YF, Gendron TF, Zhang YJ, Lin WL, D'Alton S, Sheng H, Casey MC, Tong J, Knight J, Yu X, Rademakers R, Boylan K, Hutton M, McGowan E, Dickson DW, 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 2010; 30: 10851-10859.
42. Shan X, Chiang PM, Price DL, Wong PC: Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc Natl Acad Sci USA 2010; 107: 16325-16330.
43. Zhou H, Huang C, Chen H, Wang D, Landel CP, Xia PY, Bowser R, Liu YJ, Xia XG: A transgenic rat model of neurodegeneration caused by mutation in the TDP gene. PLoS Genet 2010; 6:e1000887.
44. Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS: Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 1997; 19: 939-945. (Pubitemid 27471397)
45. Wang J, Xu G, Slunt HH, Gonzales V, Coonfield M, Fromholt D, Copeland NG, Jenkins NA, Borchelt DR: Coincident thresholds of mutant protein for paralytic disease and protein aggregation caused by restrictively expressed superoxide dismutase cDNA. Neurobiol Dis 2005; 20: 943-952. (Pubitemid 41619369)
46. Vidal M, Morris R, Grosveld F, Spanopoulou E: Tissue-specific control elements of the Thy-1 gene. Embo J 1990; 9: 833-840.
47. Caroni P: Overexpression of growth-associated proteins in the neurons of adult transgenic mice. J Neurosci Methods 1997; 71: 3-9. (Pubitemid 27145767)
48. Feng G, Mellor RH, Bernstein M, Keller-Peck C, Nguyen QT, Wallace M, Nerbonne JM, Lichtman JW, Sanes JR: Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 2000; 28: 41-51.
49. Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER: Control of memory formation through regulated expression of a CaMKII transgene. Science 1996; 274: 1678-1683. (Pubitemid 26414891)
50. Chen-Plotkin AS, Lee VM, Trojanowski JQ: TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 2010; 6: 211-220.
51. Lagier-Tourenne C, Polymenidou M, Cleveland DW: TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet 2010; 19:R46-R64.
52. Davidson Y, Kelley T, Mackenzie IR, Pickering-Brown S, Du Plessis D, Neary D, Snowden JS, Mann DM: Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta Neuropathol 2007; 113: 521-533. (Pubitemid 46672598)
53. 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 2006; 351: 602-611. (Pubitemid 44708852)
54. Magrane J, Manfredi G: Mitochondrial function, morphology, and axonal transport in amyotrophic lateral sclerosis. Antioxid Redox Signal 2009; 11: 1615-1626.
55. Johnson BS, Snead D, Lee JJ, McCaffery JM, Shorter J, Gitler AD: TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 2009; 284: 20329-20339.
56. Igaz LM, Kwong LK, Chen-Plotkin A, Winton MJ, Unger TL, Xu Y, Neumann M, Trojanowski JQ, Lee VM: Expression Of TDP-43 C-terminal fragments in vitro recapitulates pathological features of TDP-43 proteinopathies. J Biol Chem 2009; 284: 8516-8524.
57. Wu LS, Cheng WC, Hou SC, Yan YT, Jiang ST, Shen CK: TDP-43, a neuro-pathosignature factor, is essential for early mouse embryogenesis. Genesis 2010; 48: 56-62.
58. Sephton CF, Good SK, Atkin S, Dewey CM, Mayer P 3rd, Herz J, Yu G: TDP-43 is a developmentally regulated protein essential for early embryonic development. J Biol Chem 2010; 285: 6826-6834.
59. Kraemer BC, Schuck T, Wheeler JM, Robinson LC, Trojanowski JQ, Lee VM, Schellenberg GD: Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis. Acta Neuropathol 2010; 119: 409-419.
60. Ayala YM, Zago P, D'Ambrogio A, Xu YF, Petrucelli L, Buratti E, Baralle FE: Structural determinants of the cellular localization and shuttling of TDP-43. J Cell Sci 2008; 121: 3778-3785.
61. Iguchi Y, Katsuno M, Niwa J, Yamada S, Sone J, Waza M, Adachi H, Tanaka F, Nagata K, Arimura N, Watanabe T, Kaibuchi K, Sobue G: TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases. J Biol Chem 2009; 284: 22059-22066.
62. Chiang PM, Ling J, Jeong YH, Price DL, Aja SM, Wong PC: Deletion of TDP-43 downregulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc Natl Acad Sci USA 2010; 107: 16320-16324.
63. Dupuis L, Oudart H, Rene F, Gonzalez de Aguilar JL, Loeffler JP: Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci USA 2004; 101: 11159-11164. (Pubitemid 38989600)
64. Moisse K, Volkening K, Leystra-Lantz C, Welch I, Hill T, Strong MJ: Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res 2009; 1249: 202-211.
65. Lorson CL, Rindt H, Shababi M: Spinal muscular atrophy: mechanisms and therapeutic strategies. Hum Mol Genet 2010; 19:R111-R118.
66. Bose JK, Wang IF, Hung L, Tarn WY, Shen CK: TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing. J Biol Chem 2008; 283: 28852-28859.
67. Winklhofer KF, Tatzelt J, Haass C: The two faces of protein misfolding: gain-and lossof-function in neurodegenerative diseases. Embo J 2008; 27: 336-349. (Pubitemid 351161650)
68. Cairns NJ, Neumann M, Bigio EH, Holm IE, Troost D, Hatanpaa KJ, Foong C, White CL, 3rd, Schneider JA, Kretzschmar HA, Carter D, Taylor-Reinwald L, Paulsmeyer K, Strider J, Gitcho M, Goate AM, Morris JC, Mishra M, Kwong LK, Stieber A, Xu Y, Forman MS, Trojanowski JQ, Lee VM, Mackenzie IR: TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 2007; 171: 227-240. (Pubitemid 47342406)
69. Leigh PN, Whitwell H, Garofalo O, Buller J, Swash M, Martin JE, Gallo JM, Weller RO, Anderton BH: Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 1991; 114: 775-788.
70. Rothstein JD: Of mice and men: reconciling preclinical ALS mouse studies and human clinical trials. Ann Neurol 2003; 53: 423-426. (Pubitemid 36373252)
71. Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH Jr, Scott RW, Snider WD: Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet 1996; 13: 43-47. (Pubitemid 26139292)
72. Jonsson PA, Graffmo KS, Andersen PM, Brannstrom T, Lindberg M, Oliveberg M, Marklund SL: Disulphide-reduced superoxide dismutase-1 in CNS of transgenic amyotrophic lateral sclerosis models. Brain 2006; 129: 451-464. (Pubitemid 43164368)
73. Jaarsma D: Swelling and vacuolisation of mitochondria in transgenic SOD1-ALS mice: a consequence of supranormal SOD1 expression? Mitochondrion 2006; 6: 48-49; author reply 50-51.
74. Turner BJ, Talbot K: Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog Neurobiol 2008; 85: 94-134.
75. Kreutzberg GW: Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19: 312-318. (Pubitemid 26349059)
76. Kawamata T, Akiyama H, Yamada T, Mc-Geer PL: Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 1992; 140: 691-707.
77. Ince PG, Shaw PJ, Slade JY, Jones C, Hudgson P: Familial amyotrophic lateral sclerosis with a mutation in exon 4 of the Cu/Zn superoxide dismutase gene: pathological and immunocytochemical changes. Acta Neuropathol 1996; 92: 395-403. (Pubitemid 26317107)
78. Alexianu ME, Kozovska M, Appel SH: Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 2001; 57: 1282-1289. (Pubitemid 32947389)
79. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G, Cleveland DW: Onset and progression in inherited ALS determined by motor neurons and microglia. Science 2006; 312: 1389-1392. (Pubitemid 43839552)
80. Lobsiger CS, Boillee S, McAlonis-Downes M, Khan AM, Feltri ML, Yamanaka K, Cleveland DW: Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc Natl Acad Sci USA 2009; 106: 4465-4470.
81. Bilen J, Bonini NM: Drosophila as a model for human neurodegenerative disease. Annu Rev Genet 2005; 39: 153-171. (Pubitemid 43011111)
82. Feiguin F, Godena VK, Romano G, D'Ambrogio A, Klima R, Baralle FE: Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior. FEBS Lett 2009; 583: 1586-1592.
83. Lu Y, Ferris J, Gao FB: Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching. Mol Brain 2009; 2: 30.
84. Li Y, Ray P, Rao EJ, Shi C, Guo W, Chen X, Woodruff EA 3rd, Fushimi K, Wu JY: A Drosophila model for TDP-43 proteinopathy. Proc Natl Acad Sci USA 2010; 107: 3169-3174.
85. Fiesel FC, Voigt A, Weber SS, Van den Haute C, Waldenmaier A, Gorner K, Walter M, Anderson ML, Kern JV, Rasse TM, Schmidt T, Springer W, Kirchner R, Bonin M, Neumann M, Baekelandt V, Alunni-Fabbroni M, Schulz JB, Kahle PJ: Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. Embo J 2010; 29: 209-221.
86. Hanson KA, Kim SH, Wassarman DA, Tibbetts RS: Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral sclerosis (ALS). J Biol Chem 2010; 285: 11068-11072.
87. Ritson GP, Custer SK, Freibaum BD, Guinto JB, Geffel D, Moore J, Tang W, Winton MJ, Neumann M, Trojanowski JQ, Lee VM, Forman MS, Taylor JP: TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J Neurosci 2010; 30: 7729-7739.
88. Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rub U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD: Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 2010; 466: 1069-1075.