From molecule to molecule and cell to cell: Prion-like mechanisms in amyotrophic lateral sclerosis

Neurobiology of Disease

Volumn 77, Issue , 2015, Pages 257-265

  Grad, Leslie I ^a   Fernando, Sarah M ^a   Cashman, Neil R ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Amyotrophic lateral sclerosis; Exosomes; Intercellular transmission; Prion like; Propagated protein misfolding; Protein aggregation; Superoxide dismutase 1 (SOD1); TAR DNA binding protein 43 (TDP 43)

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; DNA BINDING PROTEIN; PRION; PROTEIN TDP-43; SUPEROXIDE DISMUTASE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL; GENETICS; HUMAN; METABOLISM; PATHOLOGY; PRION; PROTEIN FOLDING;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; DNA-BINDING PROTEINS; HUMANS; PRIONS; PROTEIN FOLDING; SUPEROXIDE DISMUTASE;

EID: 84930452093     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2015.02.009     Document Type: Review

References (139)

1. Aguzzi A. Cell biology: beyond the prion principle. Nature 2009, 459:924-925.
2. Aguzzi A., Rajendran L. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 2009, 64:783-790.
3. Alberti S., et al. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 2009, 137:146-158.
4. ALS Mutation Database 2007, http://reseq.biosciencedbc.jp/resequence/SearchDisease.do?targetId=1, The University of Tokyo.
5. Andersen P.M., et al. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat. Genet. 1995, 10:61-66.
6. Andersen P.M., et al. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2003, 4:62-73.
7. Arai T., et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 2006, 351:602-611.
8. Audet J.N., et al. Wild-type human SOD1 overexpression does not accelerate motor neuron disease in mice expressing murine Sod1(G86R). Neurobiol Dis 2010, 40(1):245-250.
9. Bard F., et al. Sustained levels of antibodies against Abeta in amyloid-rich regions of the CNS following intravenous dosing in human APP transgenic mice. Exp. Neurol. 2012, 238:38-43.
10. Basso M., et al. Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis. J. Biol. Chem. 2013, 288:15699-15711.
11. Beckman J.S., Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol. 1996, 271:C1424-C1437.
12. Beckman J.S., et al. ALS, SOD and peroxynitrite. Nature 1993, 364:584.
13. Beckman J.S., et al. Superoxide dismutase and the death of motoneurons in ALS. Trends Neurosci. 2001, 24:S15-S20.
14. Bendotti C., et al. Dysfunction of constitutive and inducible ubiquitin-proteasome system in amyotrophic lateral sclerosis: implication for protein aggregation and immune response. Prog. Neurobiol. 2012, 97:101-126.
15. Bosco D.A., et al. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat. Neurosci. 2010, 13:1396-1403.
16. Braak H., et al. Amyotrophic lateral sclerosis-a model of corticofugal axonal spread. Nat. Rev. Neurol. 2013, 9:708-714.
17. Bradley W.G. Updates on amyotrophic lateral sclerosis: improving patient care. Ann. Neurol. 2009, 65(Suppl. 1):S1-S2.
18. Brettschneider J., et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann. Neurol. 2013, 74:20-38.
19. Broom W.J., et al. 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 2008, 9:229-237.
20. Bruijn L.I., et al. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 1997, 18:327-338.
21. Bruijn L.I., et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 1998, 281:1851-1854.
22. Casoni F., et al. Protein nitration in a mouse model of familial amyotrophic lateral sclerosis: possible multifunctional role in the pathogenesis. J. Biol. Chem. 2005, 280:16295-16304.
23. Chia R., et al. Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis. PLoS ONE 2010, 5:e10627.
24. Chou S.M., et al. Colocalization of NOS and SOD1 in neurofilament accumulation within motor neurons of amyotrophic lateral sclerosis: an immunohistochemical study. J. Chem. Neuroanat. 1996, 10:249-258.
25. Chou S.M., et al. Role of SOD-1 and nitric oxide/cyclic GMP cascade on neurofilament aggregation in ALS/MND. J. Neurol. Sci. 1996, 139(Suppl.):16-26.
26. Clavaguera F., et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat. Cell Biol. 2009, 11:909-913.
27. Cleveland D.W. From Charcot to SOD1: mechanisms of selective motor neuron death in ALS. Neuron 1999, 24:515-520.
28. Cleveland D.W., Liu J. Oxidation versus aggregation-how do SOD1 mutants cause ALS?. Nat. Med. 2000, 6:1320-1321.
29. Cleveland D.W., Rothstein J.D. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci. 2001, 2:806-819.
30. Coleman B.M., et al. Prion-infected cells regulate the release of exosomes with distinct ultrastructural features. FASEB J. 2012, 26:4160-4173.
31. Couthouis J., et al. A yeast functional screen predicts new candidate ALS disease genes. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:20881-20890.
32. Danzer K.M., et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol. Neurodegener. 2012, 7:42.
33. Deng H.X., et al. Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:7142-7147.
34. Deng H.X., et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 2011, 477:211-215.
35. Diener T.O., et al. Viroids and prions. Proc. Natl. Acad. Sci. U. S. A. 1982, 79:5220-5224.
36. Eisele Y.S., et al. Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science 2010, 330:980-982.
37. El-Agnaf O.M., et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J. 2006, 20:419-425.
38. Elam J.S., et al. Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS. Nat. Struct. Biol. 2003, 10:461-467.
39. Elden A.C., et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 2010, 466:1069-1075.
40. Emmanouilidou E., et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J. Neurosci. 2010, 30:6838-6851.
41. Fevrier B., et al. Cells release prions in association with exosomes. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:9683-9688.
42. Forsberg K., et al. Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients. PLoS ONE 2010, 5:e11552.
43. Frost B., et al. Propagation of tau misfolding from the outside to the inside of a cell. J. Biol. Chem. 2009, 284:12845-12852.
44. Fukada K., et al. Stabilization of mutant Cu/Zn superoxide dismutase (SOD1) protein by coexpressed wild SOD1 protein accelerates the disease progression in familial amyotrophic lateral sclerosis mice. Eur. J. Neurosci. 2001, 14:2032-2036.
45. Furukawa Y., et al. Complete loss of post-translational modifications triggers fibrillar aggregation of SOD1 in the familial form of amyotrophic lateral sclerosis. J. Biol. Chem. 2008, 283:24167-24176.
46. Furukawa Y., et al. A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element (TAR) DNA-binding protein-43 inclusions. J. Biol. Chem. 2011, 286:18664-18672.
47. Furukawa Y., et al. Intracellular seeded aggregation of mutant Cu,Zn-superoxide dismutase associated with amyotrophic lateral sclerosis. FEBS Lett. 2013, 587:2500-2505.
48. Gitcho M.A., et al. TDP-43 A315T mutation in familial motor neuron disease. Ann. Neurol. 2008, 63:535-538.
49. Gitler A.D., Shorter J. RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion 2011, 5:179-187.
50. Gomes C., et al. Evidence for secretion of Cu,Zn superoxide dismutase via exosomes from a cell model of amyotrophic lateral sclerosis. Neurosci. Lett. 2007, 428:43-46.
51. Grad L.I., et al. Intermolecular transmission of superoxide dismutase 1 misfolding in living cells. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:16398-16403.
52. Grad L.I., 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, 111:3620-3625.
53. Gruzman A., et al. Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:12524-12529.
54. Guest W.C., et al. Toward a mechanism of prion misfolding and structural models of PrP(Sc): current knowledge and future directions. J. Toxicol. Environ. Health A 2011, 74:154-160.
55. Guo J.L., Lee V.M. Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J. Biol. Chem. 2011, 286:15317-15331.
56. Guo W., et al. An ALS-associated mutation affecting TDP-43 enhances protein aggregation, fibril formation and neurotoxicity. Nat. Struct. Mol. Biol. 2011, 18:822-830.
57. Gurney M.E., et al. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 1994, 264:1772-1775.
58. Haass C., Selkoe D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 2007, 8:101-112.
59. Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002, 297:353-356.
60. Hasegawa M., et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann. Neurol. 2008, 64:60-70.
61. Haverkamp L.J., et al. Natural history of amyotrophic lateral sclerosis in a database population. Validation of a scoring system and a model for survival prediction. Brain 1995, 118(Pt 3):707-719.
62. Horwich A.L., Weissman J.S. Deadly conformations-protein misfolding in prion disease. Cell 1997, 89:499-510.
63. Huang E.J., et al. Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions. Brain Pathol. 2010, 20:1069-1076.
64. Huttner W.B., et al. The granin (chromogranin/secretogranin) family. Trends Biochem. Sci. 1991, 16:27-30.
65. Irwin D.J., et al. Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol. 2013, 70:462-468.
66. Jaarsma D., et al. Human Cu/Zn superoxide dismutase (SOD1) overexpression in mice causes mitochondrial vacuolization, axonal degeneration, and premature motoneuron death and accelerates motoneuron disease in mice expressing a familial amyotrophic lateral sclerosis mutant SOD1. Neurobiol. Dis. 2000, 7:623-643.
67. Johnson B.S., et al. A yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:6439-6444.
68. Johnson B.S., et al. TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J. Biol. Chem. 2009, 284:20329-20339.
69. Kabashi E., et al. Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis?. Ann. Neurol. 2007, 62:553-559.
70. Kabashi E., et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 2008, 40:572-574.
71. Kato S., et al. New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: inclusions containing SOD1 in neurons and astrocytes. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2000, 1:163-184.
72. Kayed R., et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 2003, 300:486-489.
73. Keller S., et al. Exosomes: from biogenesis and secretion to biological function. Immunol. Lett. 2006, 107:102-108.
74. Kerman A., et al. Amyotrophic lateral sclerosis is a non-amyloid disease in which extensive misfolding of SOD1 is unique to the familial form. Acta Neuropathol. 2010, 119:335-344.
75. Kim D.K., et al. EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. J. Extracell. Vesicles 2013, 2.
76. King O.D., et al. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 2012, 1462:61-80.
77. Kwiatkowski T.J., et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323:1205-1208.
78. Lashuel H.A., et al. Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J. Mol. Biol. 2002, 322:1089-1102.
79. Legname G., et al. Strain-specified characteristics of mouse synthetic prions. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:2168-2173.
80. Lesne S., et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006, 440:352-357.
81. Liu-Yesucevitz L., et al. Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue. PLoS ONE 2010, 5:e13250.
82. Luk K.C., et al. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:20051-20056.
83. Luk K.C., et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012, 338:949-953.
84. Matias-Guiu J., et al. Superoxide dismutase: the cause of all amyotrophic lateral sclerosis?. Ann. Neurol. 2008, 64:356-357. (author reply 358).
85. Meyer-Luehmann M., et al. Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 2006, 313:1781-1784.
86. Mousavi A., Hotta Y. Glycine-rich proteins: a class of novel proteins. Appl. Biochem. Biotechnol. 2005, 120:169-174.
87. Munch C., et al. Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:3548-3553.
88. Neumann M., et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006, 314:130-133.
89. Nonaka T., et al. Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43. Hum. Mol. Genet. 2009, 18:3353-3364.
90. Nonaka T., et al. Prion-like properties of pathological TDP-43 aggregates from diseased brains. Cell Rep. 2013, 4:124-134.
91. Patino M.M., et al. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science 1996, 273:622-626.
92. Perez-Gonzalez R., et al. The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space. J. Biol. Chem. 2012, 287:43108-43115.
93. Pesiridis G.S., et al. Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis. Hum. Mol. Genet. 2009, 18:R156-R162.
94. Philips T., Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 2011, 10:253-263.
95. Phukan J., et al. Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol. 2007, 6:994-1003.
96. Pokrishevsky E., et al. Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS ONE 2012, 7:e35050.
97. Prudencio M., et al. Modulation of mutant superoxide dismutase 1 aggregation by co-expression of wild-type enzyme. J. Neurochem. 2009, 108:1009-1018.
98. Prudencio M., et al. Variation in aggregation propensities among ALS-associated variants of SOD1: correlation to human disease. Hum. Mol. Genet. 2009, 18:3217-3226.
99. Prudencio M., et al. An examination of wild-type SOD1 in modulating the toxicity and aggregation of ALS-associated mutant SOD1. Hum. Mol. Genet. 2010, 19:4774-4789.
100. Prusiner S.B. Novel proteinaceous infectious particles cause scrapie. Science 1982, 216:136-144.
101. Rakhit R., et al. Oxidation-induced misfolding and aggregation of superoxide dismutase and its implications for amyotrophic lateral sclerosis. J. Biol. Chem. 2002, 277:47551-47556.
102. Rakhit R., et al. Monomeric Cu,Zn-superoxide dismutase is a common misfolding intermediate in the oxidation models of sporadic and familial amyotrophic lateral sclerosis. J. Biol. Chem. 2004, 279:15499-15504.
103. Rakhit R., et al. An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS. Nat. Med. 2007, 13:754-759.
104. Ratovitski T., et al. Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds. Hum. Mol. Genet. 1999, 8:1451-1460.
105. Ravits J.M., La Spada A.R. ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 2009, 73:805-811.
106. Ravits J., et al. Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. Neurology 2007, 68:1571-1575.
107. Raymond G.J., et al. Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J. 2000, 19:4425-4430.
108. Reaume A.G., et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat. Genet. 1996, 13:43-47.
109. Rosen D.R. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993, 364:362.
110. Rutherford N.J., et al. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet. 2008, 4:e1000193.
111. Said Ahmed M., et al. Increased reactive oxygen species in familial amyotrophic lateral sclerosis with mutations in SOD1. J. Neurol. Sci. 2000, 176:88-94.
112. Sampathu D.M., et al. Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. Am. J. Pathol. 2006, 169:1343-1352.
113. Sekiguchi T., et al. Spreading of amyotrophic lateral sclerosis lesions-multifocal hits and local propagation?. J. Neurol. Neurosurg. Psychiatry 2014, 85:85-91.
114. Sephton C.F., et al. TDP-43 is a developmentally regulated protein essential for early embryonic development. J. Biol. Chem. 2010, 285:6826-6834.
115. Shankar G.M., et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 2008, 14:837-842.
116. Shibata N., et al. Cu/Zn superoxide dismutase-like immunoreactivity in Lewy body-like inclusions of sporadic amyotrophic lateral sclerosis. Neurosci. Lett. 1994, 179:149-152.
117. Sreedharan J., et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008, 319:1668-1672.
118. Stewart H., et al. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p. Acta Neuropathol. 2012, 123:409-417.
119. Strong M., Rosenfeld J. Amyotrophic lateral sclerosis: a review of current concepts. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2003, 4:136-143.
120. Sun Z., et al. Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS. PLoS Biol. 2011, 9:e1000614.
121. Synofzik M., et al. Mutant superoxide dismutase-1 indistinguishable from wild-type causes ALS. Hum. Mol. Genet. 2012, 21:3568-3574.
122. Tan A.Y., Manley J.L. The TET family of proteins: functions and roles in disease. J. Mol. Cell Biol. 2009, 1:82-92.
123. Taylor D.M., et al. Tryptophan 32 potentiates aggregation and cytotoxicity of a copper/zinc superoxide dismutase mutant associated with familial amyotrophic lateral sclerosis. J. Biol. Chem. 2007, 282:16329-16335.
124. Thomsen C., et al. A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins. FASEB J. 2013, 27:4965-4974.
125. Toombs J.A., et al. Compositional determinants of prion formation in yeast. Mol. Cell. Biol. 2010, 30:319-332.
126. Uptain S.M., Lindquist S. Prions as protein-based genetic elements. Annu. Rev. Microbiol. 2002, 56:703-741.
127. Urushitani M., et al. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat. Neurosci. 2006, 9:108-118.
128. Urushitani M., et al. The endoplasmic reticulum-Golgi pathway is a target for translocation and aggregation of mutant superoxide dismutase linked to ALS. FASEB J. 2008, 22:2476-2487.
129. Van Deerlin V.M., et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 2008, 7:409-416.
130. Vance C., et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323:1208-1211.
131. Wang J., et al. Fibrillar inclusions and motor neuron degeneration in transgenic mice expressing superoxide dismutase 1 with a disrupted copper-binding site. Neurobiol. Dis. 2002, 10:128-138.
132. Wang Q., et al. Protein aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival. PLoS Biol. 2008, 6:e170.
133. Wang L., et al. Wild-type SOD1 overexpression accelerates disease onset of a G85R SOD1 mouse. Hum. Mol. Genet. 2009, 18:1642-1651.
134. Wang I.F., et al. The self-interaction of native TDP-43 C terminus inhibits its degradation and contributes to early proteinopathies. Nat. Commun. 2012, 3:766.
135. Weichert A., et al. Wild-type Cu/Zn superoxide dismutase stabilizes mutant variants by heterodimerization. Neurobiol. Dis. 2013, 62:479-488.
136. Witan H., et al. Wild-type Cu/Zn superoxide dismutase (SOD1) does not facilitate, but impedes the formation of protein aggregates of amyotrophic lateral sclerosis causing mutant SOD1. Neurobiol. Dis. 2009, 36:331-342.
137. Wu C.H., et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 2012, 488:499-503.
138. Wu L.S., et al. TDP-43, a neuro-pathosignature factor, is essential for early mouse embryogenesis. Genesis 2010, 48:56-62.
139. Yokoseki A., et al. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann. Neurol. 2008, 63:538-542.