Erratum: Emerging mechanisms of molecular pathology in ALS (Journal of Clinical Investigation (2015) 125:5 (1767-1779) DOI: 10.1172/JCI71601);Emerging mechanisms of molecular pathology in ALS

Journal of Clinical Investigation

Volumn 125, Issue 5, 2015, Pages 1767-1779

  Peters, Owen M ^a   Ghasemi, Mehdi ^a   Brown, Robert H ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; DNA BINDING PROTEIN; NERVE PROTEIN; RNA BINDING PROTEIN; SUPEROXIDE DISMUTASE;

AMYOTROPHIC LATERAL SCLEROSIS; CELL INCLUSION; CYTOSKELETON; DNA BINDING; GENE MUTATION; HUMAN; MOLECULAR PATHOLOGY; MOTONEURON; NERVE FIBER TRANSPORT; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DOMAIN; REVIEW; RNA BINDING; RNA TRANSCRIPTION; RNA TRANSPORT; ANIMAL; CHEMISTRY; DEFICIENCY; GENE THERAPY; GENETIC ASSOCIATION; GENETICS; GLIA; IMMUNOLOGY; INFLAMMATION; METABOLISM; MOLECULARLY TARGETED THERAPY; MOUSE; NERVE FIBER; PATHOLOGY; PROTEIN DEGRADATION; PROTEIN PROCESSING; PROTEINOSIS; TRANSGENIC MOUSE; UBIQUITINATION; ULTRASTRUCTURE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; AXONAL TRANSPORT; AXONS; CYTOSKELETON; DNA-BINDING PROTEINS; GENETIC ASSOCIATION STUDIES; GENETIC THERAPY; HUMANS; INFLAMMATION; MICE; MICE, TRANSGENIC; MOLECULAR TARGETED THERAPY; MOTOR NEURONS; NERVE TISSUE PROTEINS; NEUROGLIA; OXIDATIVE STRESS; PROTEIN AGGREGATION, PATHOLOGICAL; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOLYSIS; RNA-BINDING PROTEINS; SUPEROXIDE DISMUTASE; UBIQUITINATION;

EID: 84929000939     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI82693     Document Type: Erratum

References (139)

1. O'Toole O, et al. Epidemiology clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004. J Neurol Neurosurg Psychiatry. 2008;79(1):30-32.
2. Armon C. Sports and trauma in amyotrophic lateral sclerosis revisited. J Neurol Sci. 2007;262(1-2):45-53.
3. Alonso A, Logroscino G, Jick SS, Hernán MA. Incidence and lifetime risk of motor neuron disease in the United Kingdom: a population-based study. Eur J Neurol. 2009;16(6):745-751.
4. Johnston CA, et al. Amyotrophic lateral sclerosis in an urban setting: a population based study of inner city London. J Neurol. 2006;253(12):1642-1643.
5. Leblond CS, Kaneb HM, Dion PA, Rouleau GA. Dissection of genetic factors associated with amyotrophic lateral sclerosis. Exp Neurol. 2014;262(pt B):91-101.
6. Sreedharan J, Brown RH Jr. Amyotrophic lateral sclerosis: Problems and prospects. Ann Neurol. 2013;74(3):309-316.
7. Ng AS, Rademakers R, Miller BL. Frontotemporal dementia: a bridge between dementia and neuromuscular disease [published online ahead of print December 30, 2014]. Ann N Y Acad Sci. doi:10.1111/nyas.12638.
8. Swinnen B, Robberecht W. The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol. 2014;10(11):661-670.
9. Leigh PN, Anderton BH, Dodson A, Gallo JM, Swash M, Power DM. Ubiquitin deposits in anterior horn cells in motor neurone disease. Neurosci Lett. 1988;93(2-3):197-203.
10. Okamoto K, Mizuno Y, Fujita Y. Bunina bodies in amyotrophic lateral sclerosis. Neuropathology. 2008;28(2):109-115.
11. Rosen DR, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(6415):59-62.
12. Radunović A, Leigh PN. ALSODatabase: database of SOD1 (and other) gene mutations in ALS on the Internet. European FALS Group and ALSOD Consortium. Amyotroph Lateral Scler Other Motor Neuron Disord. 1999;1(1):45-49.
13. Shibata N, et al. Immunohistochemical demonstration of Cu/Zn superoxide dismutase in the spinal cord of patients with familial amyotrophic lateral sclerosis. Acta Histochem Cytochem. 1993;26:619-622.
14. Borchelt DR, et al. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci U S A. 1994;91(17):8292-8296.
15. Prudencio M, Hart PJ, Borchelt DR, Andersen PM. Variation in aggregation propensities among ALS-associated variants of SOD1: correlation to human disease. Hum Mol Genet. 2009;18(17):3217-3226.
16. Chung J, Yang H, de Beus MD, Ryu CY, Cho K, Colón W. Cu/Zn superoxide dismutase can form pore-like structures. Biochem Biophys Res Commun. 2003;312(4):873-876.
17. Caughey B, Lansbury PT. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci. 2003;26:267-298.
18. Brown HH, Borchelt DR. Analysis of mutant SOD1 electrophoretic mobility by Blue Native gel electrophoresis; evidence for soluble multimeric assemblies. PLoS One. 2014;9(8):e104583.
19. Ray SS, Nowak RJ, Strokovich K, Brown RH Jr, Walz T, Lansbury PT Jr. An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis. Biochemistry. 2004;43(17):4899-4905.
20. Ray SS, Lansbury PT Jr. A possible therapeutic target for Lou Gehrig's disease. Proc Natl Acad Sci U S A. 2004;101(16):5701-5702.
21. Bosco DA, et al. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci. 2010;13(11):1396-1403.
22. Grad LI, et al. Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms. Proc Natl Acad Sci U S A. 2014;111(9):3620-3625.
23. Forsberg K, et al. Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients. PLoS One. 2010;5(7):e11552.
24. van Blitterswijk M, et al. Anti-superoxide dismutase antibodies are associated with survival in patients with sporadic amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011;12(6):430-438.
25. Estévez AG, et al. Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science. 1999;286(5449):2498-2500.
26. Beckman JS, Carson M, Smith CD, Koppenol WH. ALS, SOD and peroxynitrite. Nature. 1993;364(6438):584.
27. Tiwari A, Xu Z, Hayward LJ. Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosis. J Biol Chem. 2005;280(33):29771-29779.
28. van Zundert B, Izaurieta P, Fritz E, Alvarez FJ. Early pathogenesis in the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Cell Biochem. 2012;113(11):3301-3312.
29. Vande Velde C, et al. Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. PLoS One. 2011;6(7):e22031.
30. Vucic S, Rothstein JD, Kiernan MC. Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies. Trends Neurosci. 2014;37(8):433-442.
31. Hetz C, et al. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev. 2009;23(19):2294-2306.
32. Morfini GA, et al. Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase. PLoS One. 2013;8(6):e65235.
33. Kanning KC, Kaplan A, Henderson CE. Motor neuron diversity in development and disease. Annu Rev Neurosci. 2010;33:409-440.
34. Gurney ME, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 1994;264(5166):1772-1775.
35. Neumann M, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314(5796):130-133.
36. Lagier-Tourenne C, Polymenidou M, Cleveland DW. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet. 2010;19(R1):R46-R64.
37. Brettschneider J, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013;74(1):20-38.
38. Sreedharan J, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008;319(5870):1668-1672.
39. Daoud H, et al. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J Med Genet. 2009;46(2):112-114.
40. Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013;9(11):617-628.
41. Jonsson PA, et al. Minute quantities of misfolded mutant superoxide dismutase-1 cause amyotrophic lateral sclerosis. Brain. 2004;127(pt 1):73-88.
42. Reaume AG, et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet. 1996;13(1):43-47.
43. D'Alton S, Altshuler M, Cannon A, Dickson DW, Petrucelli L, Lewis J. Divergent phenotypes in mutant TDP-43 transgenic mice highlight potential confounds in TDP-43 transgenic modeling. PLoS One. 2014;9(1):e86513.
44. Gendron TF, Petrucelli L. Rodent models of TDP-43 proteinopathy: investigating the mechanisms of TDP-43-mediated neurodegeneration. J Mol Neurosci. 2011;45(3):486-499.
45. Xu YF, et al. Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci. 2010;30(32):10851-10859.
46. Wu LS, Cheng WC, Shen CK. Targeted depletion of TDP-43 expression in the spinal cord motor neurons leads to the development of amyotrophic lateral sclerosis-like phenotypes in mice. J Biol Chem. 2012;287(33):27335-27344.
47. Kwiatkowski TJ Jr, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009;323(5918):1205-1208.
48. Vance C, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323(5918):1208-1211.
49. Neumann M, Roeber S, Kretzschmar HA, Rademakers R, Baker M, Mackenzie IR. Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathologica. 2009;118(5):605-616.
50. Deng HX, et al. FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann Neurol. 2010;67(6):739-748.
51. Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA, Mackenzie IR. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain. 2009;132(pt 11):2922-2931.
52. Kuroda M, et al. Male sterility and enhanced radiation sensitivity in TLS(-/-) mice. EMBO J. 2000;19(3):453-462.
53. Huang C, et al. FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PLoS Genet. 2011;7(3):e1002011.
54. Dejesus-Hernandez M, et al. Expanded GGGGCC hexanucleotide repeat in non-coding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72(2):245-256.
55. Renton AE, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72(2):257-268.
56. Gijselinck I, Van Langenhove T, van der Zee J, Sleegers K, Philtjens S, et al. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol. 2012;11(1): 54-65.
57. Marat AL, Dokainish H, McPherson PS. DENN domain proteins: regulators of Rab GTPases. J Biol Chem. 2011;286(16):13791-13800.
58. van Blitterswijk M, et al. Association between repeat sizes and clinical and pathological characteristics in carriers of C9ORF72 repeat expansions (Xpansize-72): a cross-sectional cohort study. Lancet Neurol. 2013;12(10):978-988.
59. Cooper-Knock J, et al. C9ORF72 transcription in a frontotemporal dementia case with two expanded alleles. Neurology. 2013;81(19):1719-1721.
60. Fratta P, et al. Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia. Acta Neuropathol. 2013;126(3):401-409.
61. Lee YB, et al. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep. 2013;5(5):1178-1186.
62. Donnelly CJ, et al. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron. 2013;80(2):415-428.
63. Lagier-Tourenne C, et al. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci U S A. 2013;110(47):E4530-E4539.
64. Almeida S, et al. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 2013;126(3):385-399.
65. Sareen D, et al. Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med. 2013;5(208):208ra149.
66. Al-Sarraj S, et al. 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. 2011;122(6):691-702.
67. Collins M, et al. 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. 2012;124(5):717-732.
68. Mori K, et al. hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations. Acta Neuropathol. 2013;125(3):413-423.
69. Ash PE, et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron. 2013;77(4):639-646.
70. Zu T, et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci U S A. 2011;108(1):260-265.
71. Gendron TF, et al. Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS. Acta Neuropathol. 2013;126(6):829-844.
72. Mori K, et al. Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol. 2013;126(6):881-893.
73. Mori K, et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science. 2013;339(6125):1335-1338.
74. Mizielinska S, et al. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science. 2014;345(6201):1192-1194.
75. Wen X, et al. Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death. Neuron. 2014;84(6):1213-1225.
76. Watts GD, et al. Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Clin Genet. 2007;72(5):420-426.
77. Deng HX, et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature. 2011;477(7363):211-215.
78. Gonzalez-Perez P, et al. Association of UBQLN1 mutation with Brown-Vialetto-Van Laere syndrome but not typical ALS. Neurobiol Dis. 2012;48(3):391-398.
79. Fecto F, et al. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol. 2011;68(11):1440-1446.
80. Teyssou E, et al. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol. 2013;125(4):511-522.
81. Shimizu H, et al. Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene. Acta Neuropathol. 2013;126(3):453-459.
82. Chen Y, et al. SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35(3):726.e7-e9.
83. Bredesen DE, Ellerby LM, Hart PJ, Wiedau-Pazos M, Valentine JS. Do post-translational modifications of CuZnSOD lead to sporadic amyotrophic lateral sclerosis? Ann Neurol. 1997;42(2):135-137.
84. Münch C, Bertolotti A. Self-propagation and transmission of misfolded mutant SOD1: prion or prion-like phenomenon? Cell Cycle. 2011;10(11):1711.
85. Alberti S, Halfmann R, King O, Kapila A, Lindquist S. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell. 2009;137(1):146-158.
86. Cushman M, Johnson BS, King OD, Gitler AD, Shorter J. Prion-like disorders: blurring the divide between transmissibility and infectivity. J Cell Sci. 2010;123(pt 8):1191-1201.
87. Gitler AD, Shorter J. RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion. 2011;5(3):179-187.
88. King OD, Gitler AD, Shorter J. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 2012;1462:61-80.
89. Li YR, King OD, Shorter J, Gitler AD. Stress granules as crucibles of ALS pathogenesis. J Cell Biol. 2013;201(3):361-372.
90. Couthouis J, et al. A yeast functional screen predicts new candidate ALS disease genes. Proc Natl Acad Sci U S A. 2011;108(52):20881-20890.
91. Couthouis J, et al. Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet. 2012;21(13):2899-2911.
92. Ticozzi N, et al. Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(3):285-290.
93. Kim HJ, et al. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013;495(7442):467-473.
94. Chesi A, et al. Exome sequencing to identify de novo mutations in sporadic ALS trios. Nat Neurosci. 2013;16(7):851-855.
95. Prusiner SB. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet. 2013;47:601-623.
96. Polymenidou M, Cleveland DW. The seeds of neurodegeneration: prion-like spreading in ALS. Cell. 2011;147(3):498-508.
97. Bosco DA, et al. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum Mol Genet. 2010;19(21):4160-4175.
98. 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 U S A. 2008;105(10):3785-3789.
99. Dormann D, et al. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J. 2010;29(16):2841-2857.
100. Colombrita C, et al. TDP-43 is recruited to stress granules in conditions of oxidative insult. J Neurochem. 2009;111(4):1051-1061.
101. Buratti E, Dörk T, Zuccato E, Pagani F, Romano M, Baralle FE. Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J. 2001;20(7):1774-1784.
102. Buratti E, Brindisi A, Giombi M, Tisminetzky S, Ayala YM, Baralle FE. TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J Biol Chem. 2005;280(45):37572-37584.
103. Arnold ES, et al. 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. 2013;110(8):E736-E745.
104. Mankodi A, Teng-Umnuay P, Krym M, Henderson D, Swanson M, Thornton CA. Ribonuclear inclusions in skeletal muscle in myotonic dystrophy types 1 and 2. Ann Neurol. 2003;54(6):760-768.
105. Figlewicz DA, et al. Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet. 1994;3(10):1757-1761.
106. Tomkins J, et al. Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport. 1998;9(17):3967-3970.
107. Al-Chalabi A, et al. Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet. 1999;8(2):157-164.
108. Gros-Louis F, et al. A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J Biol Chem. 2004;279(44):45951-45956.
109. Leung CL, et al. A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis. Brain Pathol. 2004;14(3):290-296.
110. Corrado L, et al. A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient. Neurobiol Aging. 2011;32(3):552.e-e6.
111. Corbo M, Hays AP. Peripherin and neurofilament protein coexist in spinal spheroids of motor neuron disease. J Neuropathol Exp Neurol. 1992;51(5):531-537.
112. Wu CH, et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012;488(7412):499-503.
113. Van Hoecke A, et al. EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat Med. 2012;18(9):1418-1422.
114. Puls I, et al. Mutant dynactin in motor neuron disease. Nat Genet. 2003;33(4):455-456.
115. Laird FM, et al. Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking. J Neurosci. 2008;28(9):1997-2005.
116. Landers JE, et al. Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009;106(22):9004-9009.
117. van Doormaal PT, et al. Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study. Neurobiol Aging. 2014;35(10):2420.e13-e14.
118. Dupuis L, et al. Differential screening of mutated SOD1 transgenic mice reveals early upregulation of a fast axonal transport component in spinal cord motor neurons. Neurobiol Dis. 2000;7(4):274-285.
119. Nishimura AL, et al. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet. 2004;75(5):822-831.
120. Tsuda H, et al. The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell. 2008;133(6):963-977.
121. Forrest S, et al. Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis. Hum Mol Genet. 2013;22(13):2689-2704.
122. Clement AM, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science. 2003;302(5642):113-117.
123. Yamanaka K, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci. 2008;11(3):251-253.
124. Boillée S, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312(5778):1389-1392.
125. Kang SH, et al. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nat Neurosci. 2013;16(5):571-579.
126. Lobsiger CS, et al. Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc Natl Acad Sci U S A. 2009;106(11):4465-4470.
127. Xiao Q, et al. Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia. J Neurochem. 2007;102(6):2008-2019.
128. Beers DR, et al Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006;103(43):16021-16026.
129. Henkel JS, et al. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med. 2013;5(1):64-79.
130. Zhao W, Beers DR, Liao B, Henkel JS, Appel SH. Regulatory T lymphocytes from ALS mice suppress microglia and effector T lymphocytes through different cytokine-mediated mechanisms. Neurobiol Dis. 2012;48(3):418-428.
131. Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007;10(5):608-614.
132. Haidet-Phillips AM, et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol. 2011;29(9):824-828.
133. Nagai M, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci. 2007;10(5):615-622.
134. de Boer AS, Koszka K, Kiskinis E, Suzuki N, Davis-Dusenbery BN, Eggan K. Genetic validation of a therapeutic target in a mouse model of ALS. Sci Transl Med. 2014;6(248):248ra104.
135. Miller TM, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013;12(5):435-442.
136. Urushitani M, Ezzi SA, Julien JP. Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2007;104(7):2495-2500.
137. Ju S, et al. A yeast model of FUS/TLS-dependent cytotoxicity. PLoS Biol. 2011;9(4):e1001052.
138. Jackson KL, et al. Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther. 2015;22(1):20-28.
139. Peters O, Brown RH Jr. Amyotrophic lateral sclerosis. In: Zigmond MJ, Coyle JT, Rowland LP, eds. Neurology of Brain Disorders. Waltham, Massachusetts, USA: Academic Press; 2014:262-280.