TDP 43

Summary

Gene Symbol: TDP 43
Description: TAR DNA binding protein
Alias: ALS10, TDP-43, TAR DNA-binding protein 43, TAR DNA-binding protein-43
Species: human
Products:     TDP 43

Top Publications

  1. Udan Johns M, Bengoechea R, Bell S, Shao J, Diamond M, True H, et al. Prion-like nuclear aggregation of TDP-43 during heat shock is regulated by HSP40/70 chaperones. Hum Mol Genet. 2014;23:157-70 pubmed publisher
  2. Inukai Y, Nonaka T, Arai T, Yoshida M, Hashizume Y, Beach T, et al. Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS. FEBS Lett. 2008;582:2899-904 pubmed publisher
    ..Analysis of postmortem changes of TDP-43 revealed that the amounts of Sarkosyl-insoluble, urea-soluble full-length TDP-43 and a 35kDa N-terminal fragment increased time-dependently. ..
  3. Strong M, Volkening K, Hammond R, Yang W, Strong W, Leystra Lantz C, et al. TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci. 2007;35:320-7 pubmed
    ..TDP43 is a unique hNFL mRNA-binding protein that is altered in its somatotopic localization in ALS spinal motor neurons and potentially contributes to the formation of NF aggregates in ALS through alterations in NF stoichiometry. ..
  4. Schumacher A, Friedrich P, Diehl Schmid J, Ibach B, Perneczky R, Eisele T, et al. No association of TDP-43 with sporadic frontotemporal dementia. Neurobiol Aging. 2009;30:157-9 pubmed
    ..There is no evidence, that common variants in TDP-43 confer a strong risk to the development of sporadic FTD. ..
  5. Pokrishevsky E, Grad L, Yousefi M, Wang J, Mackenzie I, Cashman N. Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS ONE. 2012;7:e35050 pubmed publisher
    ..The identification of a final common pathway in the molecular pathogenesis of ALS provides a treatment target for this devastating disease. ..
  6. Alami N, Smith R, Carrasco M, Williams L, Winborn C, Han S, et al. Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. Neuron. 2014;81:536-543 pubmed publisher
    ..Thus, TDP-43 mutations that cause ALS lead to partial loss of a novel cytoplasmic function of TDP-43. ..
  7. Gitcho M, Baloh R, Chakraverty S, Mayo K, Norton J, Levitch D, et al. TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol. 2008;63:535-8 pubmed publisher
    ..The discovery of a missense mutation in TDP-43 in a family with dominantly inherited motor neuron disease provides evidence of a direct link between altered TDP-43 function and neurodegeneration. ..
  8. Bentmann E, Neumann M, Tahirovic S, Rodde R, Dormann D, Haass C. Requirements for stress granule recruitment of fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43). J Biol Chem. 2012;287:23079-94 pubmed publisher
  9. Lagier Tourenne C, Polymenidou M, Hutt K, Vu A, Baughn M, Huelga S, et al. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci. 2012;15:1488-97 pubmed publisher

More Information

Publications182 found, 100 shown here

  1. Van Deerlin V, Leverenz J, Bekris L, Bird T, Yuan W, Elman L, et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 2008;7:409-16 pubmed publisher
    ..National Institutes of Health (AG10124, AG17586, AG005136-22, PO1 AG14382), Department of Veterans Affairs, Friedrich-Baur Stiftung (0017/2007), US Public Health Service, ALS Association, and Fundació 'la Caixa'. ..
  2. Mompeán M, Buratti E, Guarnaccia C, Brito R, Chakrabartty A, Baralle F, et al. "Structural characterization of the minimal segment of TDP-43 competent for aggregation". Arch Biochem Biophys. 2014;545:53-62 pubmed publisher
    ..Our results provide a better understanding of TDP-43 aggregation process and will be useful to design effectors capable to modulate its progression. ..
  3. Gitcho M, Bigio E, Mishra M, Johnson N, Weintraub S, Mesulam M, et al. TARDBP 3'-UTR variant in autopsy-confirmed frontotemporal lobar degeneration with TDP-43 proteinopathy. Acta Neuropathol. 2009;118:633-45 pubmed publisher
    ..In summary, TARDBP variants may result in clinically and neuropathologically heterogeneous phenotypes linked by a common molecular pathology called TDP-43 proteinopathy. ..
  4. Iida A, Kamei T, Sano M, Oshima S, Tokuda T, Nakamura Y, et al. Large-scale screening of TARDBP mutation in amyotrophic lateral sclerosis in Japanese. Neurobiol Aging. 2012;33:786-90 pubmed publisher
    ..The estimated frequency of the TARDBP mutation in sporadic ALS is 0.29% in Japanese. The mutation frequency in familial ALS in Japanese is also similar to that in Caucasian, and is ∼10 times higher than that in Japanese sporadic ALS. ..
  5. Cohen T, Hwang A, Unger T, Trojanowski J, Lee V. Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking. EMBO J. 2012;31:1241-52 pubmed publisher
    ..Thus, TDP-43 is dynamically regulated by a redox regulatory switch that links oxidative stress to the modulation of TDP-43 and its downstream targets. ..
  6. Avendaño Vázquez S, Dhir A, Bembich S, Buratti E, Proudfoot N, Baralle F. Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection. Genes Dev. 2012;26:1679-84 pubmed publisher
    ..Overall, we uncover complex interplay between transcription, splicing, and 3' end processing to effect autoregulation of TDP-43. ..
  7. Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y, et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol. 2008;64:60-70 pubmed publisher
    ..Phosphorylation-specific antibodies will be powerful tools for the investigation of these disorders. ..
  8. Sephton C, Cenik B, Cenik B, Herz J, Yu G. TDP-43 in central nervous system development and function: clues to TDP-43-associated neurodegeneration. Biol Chem. 2012;393:589-94 pubmed publisher
    ..TDP-43 RNA targets and protein interactions have now been identified, and in vivo evidence shows that TDP-43 is essential in CNS development and function. This review will highlight aspects of these findings. ..
  9. Tong J, Huang C, Bi F, Wu Q, Huang B, Zhou H. XBP1 depletion precedes ubiquitin aggregation and Golgi fragmentation in TDP-43 transgenic rats. J Neurochem. 2012;123:406-16 pubmed publisher
    ..Although it remains to determine how mutation of TDP-43 leads to the failure of the UPR, our data demonstrate that failure of the UPR is implicated in TDP-43 pathogenesis. ..
  10. Brettschneider J, Del Tredici K, Toledo J, Robinson J, Irwin D, Grossman M, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013;74:20-38 pubmed publisher
    ..Moreover, the finding that pTDP-43 pathology develops in the prefrontal cortex as part of an ongoing disease process could account for the development of executive cognitive deficits in ALS. ..
  11. Chang H, Hou S, Way T, Wong C, Wang I. Heat-shock protein dysregulation is associated with functional and pathological TDP-43 aggregation. Nat Commun. 2013;4:2757 pubmed publisher
    ..In summary, our study suggests that a common mechanism could be involved in the pathogenesis of conformational diseases that result from HSP dysregulation. ..
  12. Buratti E, Baralle F. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci. 2008;13:867-78 pubmed
    ..The aim of this work is to provide the basic facts about TDP-43 an assessment of the multiple functions ascribed to this protein. ..
  13. Pesiridis G, Tripathy K, Tanik S, Trojanowski J, Lee V. A "two-hit" hypothesis for inclusion formation by carboxyl-terminal fragments of TDP-43 protein linked to RNA depletion and impaired microtubule-dependent transport. J Biol Chem. 2011;286:18845-55 pubmed publisher
    ..Our data support a "two-hit" mechanism of CTF aggregation dependent on TDP-43 cleavage. ..
  14. King A, Al Sarraj S, Troakes C, Smith B, Maekawa S, Iovino M, et al. Mixed tau, TDP-43 and p62 pathology in FTLD associated with a C9ORF72 repeat expansion and p.Ala239Thr MAPT (tau) variant. Acta Neuropathol. 2013;125:303-10 pubmed publisher
  15. Rayaprolu S, Fujioka S, Traynor S, Soto Ortolaza A, Petrucelli L, Dickson D, et al. TARDBP mutations in Parkinson's disease. Parkinsonism Relat Disord. 2013;19:312-5 pubmed publisher
    ..Our findings widen the phenotypic presentation for the TDP-43 p.N267S substitution and support a possible role for rare TDP-43 mutations presenting with Parkinson's disease. ..
  16. Rutherford N, Zhang Y, Baker M, Gass J, Finch N, Xu Y, et al. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet. 2008;4:e1000193 pubmed publisher
  17. Olive M, Janué A, Moreno D, Gamez J, Torrejón Escribano B, Ferrer I. TAR DNA-Binding protein 43 accumulation in protein aggregate myopathies. J Neuropathol Exp Neurol. 2009;68:262-73 pubmed publisher
  18. Austin J, Wright G, Watanabe S, Grossmann J, Antonyuk S, Yamanaka K, et al. Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to aggregation and have increased stability and half-life. Proc Natl Acad Sci U S A. 2014;111:4309-14 pubmed publisher
    ..These results contrast our perception of neurodegenerative diseases as misfolded proteinopathies and delineate a novel path from the molecular characteristics of mutant TDP-43 to aberrant cellular effects and patient phenotype. ..
  19. Wang Y, Kuo P, Chiang C, Liang J, Chen Y, Wang S, et al. The truncated C-terminal RNA recognition motif of TDP-43 protein plays a key role in forming proteinaceous aggregates. J Biol Chem. 2013;288:9049-57 pubmed publisher
  20. Yang C, Tan W, Whittle C, Qiu L, Cao L, Akbarian S, et al. The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PLoS ONE. 2010;5:e15878 pubmed publisher
    b>TAR DNA binding protein 43 KD (TDP-43) is an essential gene that regulates gene transcription, mRNA splicing and stability...
  21. Shiga A, Ishihara T, Miyashita A, Kuwabara M, Kato T, Watanabe N, et al. Alteration of POLDIP3 splicing associated with loss of function of TDP-43 in tissues affected with ALS. PLoS ONE. 2012;7:e43120 pubmed publisher
    ..Our results suggest a loss of TDP-43 function in tissues affected with ALS, supporting the hypothesis that a loss of function of TDP-43 underlies the pathogenesis of ALS. ..
  22. Robinson J, Geser F, Stieber A, Umoh M, Kwong L, Van Deerlin V, et al. TDP-43 skeins show properties of amyloid in a subset of ALS cases. Acta Neuropathol. 2013;125:121-31 pubmed publisher
  23. Kühnlein P, Sperfeld A, Vanmassenhove B, Van Deerlin V, Lee V, Trojanowski J, et al. Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations. Arch Neurol. 2008;65:1185-9 pubmed publisher
    ..Mutations in TARDBP are a rare cause of familial non-SOD1 ALS. The identification of TARDBP mutations provides strong evidence for a direct link between TDP-43 dysfunction and neurodegeneration in ALS. ..
  24. Nishimoto Y, Ito D, Yagi T, Nihei Y, Tsunoda Y, Suzuki N. Characterization of alternative isoforms and inclusion body of the TAR DNA-binding protein-43. J Biol Chem. 2010;285:608-19 pubmed publisher
    ..Our findings provide new biological and pathological insight into the development of TDP-43 proteinopathies. ..
  25. Xiong H, Wang J, Sun Y, Wu J, Chen Y, Qiao K, et al. Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis. BMC Med Genet. 2010;11:8 pubmed publisher
    ..The present data have extended the spectrum of TARDBP mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients. ..
  26. Tamaoka A, Arai M, Itokawa M, Arai T, Hasegawa M, Tsuchiya K, et al. TDP-43 M337V mutation in familial amyotrophic lateral sclerosis in Japan. Intern Med. 2010;49:331-4 pubmed
    ..In conclusion, a characteristic clinical phenotype of familial ALS with initial bulbar symptoms occurred in this family with TDP-43 M337V substitution, the pathomechanism of which should be elucidated. ..
  27. Tanji K, Zhang H, Mori F, Kakita A, Takahashi H, Wakabayashi K. p62/sequestosome 1 binds to TDP-43 in brains with frontotemporal lobar degeneration with TDP-43 inclusions. J Neurosci Res. 2012;90:2034-42 pubmed publisher
    ..Our results suggest that the interaction of TDP-43 and p62 is disrupted and may participate in the pathogenesis of TDP-43 proteinopathy...
  28. Gallone S, Giordana M, Scarpini E, Rainero I, Rubino E, Fenoglio P, et al. Absence of TARDBP gene mutations in an italian series of patients with frontotemporal lobar degeneration. Dement Geriatr Cogn Disord. 2009;28:239-43 pubmed publisher
    ..Hence, pathogenic mutations were not identified in any of the FTLD cases. Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD. ..
  29. Lin W, Castanedes Casey M, Dickson D. Transactivation response DNA-binding protein 43 microvasculopathy in frontotemporal degeneration and familial Lewy body disease. J Neuropathol Exp Neurol. 2009;68:1167-76 pubmed publisher
    ..These data suggest that these processes are astrocytic end-feet with abnormal TDP-43 fibrillary inclusions. The significance of this novel TDP-43 microvasculopathy on blood-brain barrier integrity warrants further investigation...
  30. Arai T, Mackenzie I, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K, et al. Phosphorylated TDP-43 in Alzheimer's disease and dementia with Lewy bodies. Acta Neuropathol. 2009;117:125-36 pubmed publisher
    ..There may be genetic factors, such as mutations or genetic variants of PGRN underlying the co-occurrence of abnormal deposition of TDP-43, tau and alpha-synuclein. ..
  31. Igaz L, Kwong L, Chen Plotkin A, Winton M, Unger T, Xu Y, et al. Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies. J Biol Chem. 2009;284:8516-24 pubmed publisher
    ..Thus, our results show that TDP-43 CTF expression recapitulates key biochemical features of pathological TDP-43 and support the hypothesis that the generation of TDP-43 CTFs is an important step in the pathogenesis of FTLD-U and ALS. ..
  32. Kametani F, Nonaka T, Suzuki T, Arai T, Dohmae N, Akiyama H, et al. Identification of casein kinase-1 phosphorylation sites on TDP-43. Biochem Biophys Res Commun. 2009;382:405-9 pubmed publisher
    ..Interestingly, 18 of them were located in the C-terminal glycine-rich region of TDP-43. Our results indicate that CK1-mediated phosphorylation may play a role in the pathogenesis of these diseases. ..
  33. Chang C, Chiang M, Toh E, Chang C, Huang T. Molecular mechanism of oxidation-induced TDP-43 RRM1 aggregation and loss of function. FEBS Lett. 2013;587:575-82 pubmed publisher
    ..Thus, oxidation-induced conformational change of RRM1 plays a key role in TDP-43 aggregation and disease progression...
  34. Wilson R, Yu L, Trojanowski J, Chen E, Boyle P, Bennett D, et al. TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol. 2013;70:1418-24 pubmed publisher
    ..The results suggest that TDP-43 is an important brain pathology underlying cognitive decline and dementia in old age. ..
  35. Igaz L, Kwong L, Lee E, Chen Plotkin A, Swanson E, Unger T, et al. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Invest. 2011;121:726-38 pubmed publisher
    ..Our data suggest that perturbation of endogenous nuclear TDP-43 results in loss of normal TDP-43 function(s) and gene regulatory pathways, culminating in degeneration of selectively vulnerable affected neurons. ..
  36. Fujishiro H, Uchikado H, Arai T, Hasegawa M, Akiyama H, Yokota O, et al. Accumulation of phosphorylated TDP-43 in brains of patients with argyrophilic grain disease. Acta Neuropathol. 2009;117:151-8 pubmed publisher
  37. Sun Z, Diaz Z, Fang X, Hart M, Chesi A, Shorter J, et al. Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS. PLoS Biol. 2011;9:e1000614 pubmed publisher
    ..Our findings suggest that TDP-43 and FUS, though similar RNA-binding proteins, aggregate and confer disease phenotypes via distinct mechanisms. These differences will likely have important therapeutic implications. ..
  38. Fiesel F, Voigt A, Weber S, Van den Haute C, Waldenmaier A, Görner K, et al. Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. EMBO J. 2010;29:209-21 pubmed publisher
    ..In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis. ..
  39. Nozaki I, Arai M, Takahashi K, Hamaguchi T, Yoshikawa H, Muroishi T, et al. Familial ALS with G298S mutation in TARDBP: a comparison of CSF tau protein levels with those in sporadic ALS. Intern Med. 2010;49:1209-12 pubmed
    ..The elevated CSF-tau level might be related to the damage of neurons exhibiting a large number of TDP-43 inclusions in familial ALS with this mutation. ..
  40. Kabashi E, Valdmanis P, Dion P, Spiegelman D, McConkey B, Vande Velde C, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet. 2008;40:572-4 pubmed publisher
    ..These findings further corroborate that TDP-43 is involved in ALS pathogenesis. ..
  41. Nakashima Yasuda H, Uryu K, Robinson J, Xie S, Hurtig H, Duda J, et al. Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol. 2007;114:221-9 pubmed
    ..This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders. ..
  42. Guerreiro R, Schymick J, Crews C, Singleton A, Hardy J, Traynor B. TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis. PLoS ONE. 2008;3:e2450 pubmed publisher
    ..Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American. ..
  43. Kryndushkin D, Wickner R, Shewmaker F. FUS/TLS forms cytoplasmic aggregates, inhibits cell growth and interacts with TDP-43 in a yeast model of amyotrophic lateral sclerosis. Protein Cell. 2011;2:223-36 pubmed publisher
    ..Moreover, the biophysical properties of FUS aggregates in yeast are distinctly different from many amyloidogenic proteins, suggesting they are not composed of amyloid. ..
  44. Bentmann E, Haass C, Dormann D. Stress granules in neurodegeneration--lessons learnt from TAR DNA binding protein of 43 kDa and fused in sarcoma. FEBS J. 2013;280:4348-70 pubmed publisher
    ..We propose that pathological inclusions containing RNA-binding proteins, such as TDP-43 and FUS, might arise from SGs and discuss how SGs might contribute to neurodegeneration via toxic gain or loss-of-function mechanisms. ..
  45. Neumann M, Kwong L, Lee E, Kremmer E, Flatley A, Xu Y, et al. Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol. 2009;117:137-49 pubmed publisher
  46. Lagier Tourenne C, Cleveland D. Rethinking ALS: the FUS about TDP-43. Cell. 2009;136:1001-4 pubmed publisher
    ..TDP-43 and FUS/TLS have striking structural and functional similarities, implicating alterations in RNA processing as a key event in ALS pathogenesis. ..
  47. Kovacs G, Murrell J, Horvath S, Haraszti L, Majtenyi K, Molnar M, et al. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov Disord. 2009;24:1843-7 pubmed publisher
    ..This is the first report of a TARDBP variation associated with a neurodegenerative syndrome other than ALS...
  48. Herman A, Khandelwal P, Stanczyk B, Rebeck G, Moussa C. ?-amyloid triggers ALS-associated TDP-43 pathology in AD models. Brain Res. 2011;1386:191-9 pubmed publisher
    ..These data indicate an overlap in TDP-43 pathology between AD and ALS-FTLD and suggest that A? triggers modifications of TDP-43. ..
  49. Kwong L, Neumann M, Sampathu D, Lee V, Trojanowski J. TDP-43 proteinopathy: the neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol. 2007;114:63-70 pubmed
  50. Braun R, Sommer C, Carmona Gutierrez D, Khoury C, Ring J, Buttner S, et al. Neurotoxic 43-kDa TAR DNA-binding protein (TDP-43) triggers mitochondrion-dependent programmed cell death in yeast. J Biol Chem. 2011;286:19958-72 pubmed publisher
    ..These data demonstrate that mitochondria and oxidative stress are important to TDP-43-triggered cell death in yeast and may suggest a similar role in human TDP-43 pathologies. ..
  51. Mackness B, Tran M, McClain S, Matthews C, Zitzewitz J. Folding of the RNA recognition motif (RRM) domains of the amyotrophic lateral sclerosis (ALS)-linked protein TDP-43 reveals an intermediate state. J Biol Chem. 2014;289:8264-76 pubmed publisher
    ..The intermediate state may also serve as a molecular hazard linking productive folding and function with pathological misfolding and aggregation that may contribute to disease. ..
  52. Kim S, Shanware N, Bowler M, Tibbetts R. Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA. J Biol Chem. 2010;285:34097-105 pubmed publisher
  53. Lanson N, Maltare A, King H, Smith R, Kim J, Taylor J, et al. A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43. Hum Mol Genet. 2011;20:2510-23 pubmed publisher
  54. Shiina Y, Arima K, Tabunoki H, Satoh J. TDP-43 dimerizes in human cells in culture. Cell Mol Neurobiol. 2010;30:641-52 pubmed publisher
    ..These results suggest that the 86-kDa band represents dimerized TDP-43 expressed constitutively in normal cells under physiological conditions. ..
  55. Chiò A, Borghero G, Pugliatti M, Ticca A, Calvo A, Moglia C, et al. Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Arch Neurol. 2011;68:594-8 pubmed publisher
    ..The TARDBP p.A382T missense mutation accounts for approximately one-third of all ALS cases in this island population. These patients share a large risk haplotype across the TARDBP locus, indicating that they have a common ancestor. ..
  56. Suzuki H, Lee K, Matsuoka M. TDP-43-induced death is associated with altered regulation of BIM and Bcl-xL and attenuated by caspase-mediated TDP-43 cleavage. J Biol Chem. 2011;286:13171-83 pubmed publisher
    ..These results suggest that disease-related activation of caspases may attenuate TDP-43-induced toxicity by promoting TDP-43 cleavage. ..
  57. Ayala V, Granado Serrano A, Cacabelos D, Naudi A, Ilieva E, Boada J, et al. Cell stress induces TDP-43 pathological changes associated with ERK1/2 dysfunction: implications in ALS. Acta Neuropathol. 2011;122:259-70 pubmed publisher
    ..These results demonstrate that cellular stressors are key factors in neurodegeneration associated with TDP-43 and disclose the identity of ERK1/2 as novel players in the pathogenesis of ALS. ..
  58. Gijselinck I, Sleegers K, Engelborghs S, Robberecht W, Martin J, Vandenberghe R, et al. Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS. Neurobiol Aging. 2009;30:1329-31 pubmed
    ..Our data implicate that TDP-43 has no primary genetic role in the pathophysiological mechanisms underlying central nervous system neurodegeneration in these diseases. ..
  59. Che M, Jiang Y, Xie Y, Jiang L, Hu H. Aggregation of the 35-kDa fragment of TDP-43 causes formation of cytoplasmic inclusions and alteration of RNA processing. FASEB J. 2011;25:2344-53 pubmed publisher
    ..This suggests that fragmentation of TDP-43 leads to cellular redistribution, inclusion body formation, and altered RNA processing, which are implicated in the molecular pathogenesis of ALS and FTLD. ..
  60. Fujita Y, Mizuno Y, Takatama M, Okamoto K. Anterior horn cells with abnormal TDP-43 immunoreactivities show fragmentation of the Golgi apparatus in ALS. J Neurol Sci. 2008;269:30-4 pubmed publisher
    ..These results suggest that neurons with abnormal TDP-43 immunoreactivities are associated with dysfunction of the secretory pathway in motor neurons. ..
  61. Huang C, Tong J, Bi F, Zhou H, Xia X. Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats. J Clin Invest. 2012;122:107-18 pubmed publisher
    ..Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS...
  62. Watanabe S, Kaneko K, Yamanaka K. Accelerated disease onset with stabilized familial amyotrophic lateral sclerosis (ALS)-linked mutant TDP-43 proteins. J Biol Chem. 2013;288:3641-54 pubmed publisher
    ..These results suggest that chronically increased stability of mutant or wild-type TDP-43 proteins results in a gain of toxicity through abnormal proteostasis. ..
  63. Stallings N, Puttaparthi K, Luther C, Burns D, Elliott J. Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol Dis. 2010;40:404-14 pubmed publisher
    ..Transgenic mouse lines expressing untagged mutant and wild type TDP-43 under the same promoter represent a powerful new model system for studying TDP-43 proteinopathies in vivo. ..
  64. Mackenzie I, Rademakers R, Neumann M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol. 2010;9:995-1007 pubmed publisher
    ..Nonetheless, TDP-43 and FUS are promising candidates for the development of novel biomarker assays and targeted therapies. ..
  65. Chiang H, Andersen P, Tysnes O, Gredal O, Christensen P, Graff C. Novel TARDBP mutations in Nordic ALS patients. J Hum Genet. 2012;57:316-9 pubmed publisher
    ..The mutation frequency in TARDBP in Nordic ALS patients was 1.7%. The ALS cohort was highly selected for a positive family history suggesting that mutations in TARDBP generally are a rare cause of ALS in Nordic countries. ..
  66. Corrado L, Ratti A, Gellera C, Buratti E, Castellotti B, Carlomagno Y, et al. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum Mutat. 2009;30:688-94 pubmed publisher
    ..In conclusion, this report contributes to the demonstration of the causative role of the TARDBP gene in ALS pathogenesis and indicates that mutations may affect the stability of the protein even in nonneuronal tissues. ..
  67. Benajiba L, Le Ber I, Camuzat A, Lacoste M, Thomas Anterion C, Couratier P, et al. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol. 2009;65:470-3 pubmed publisher
    ..We now describe TARDBP mutations in two patients with FTLD-MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP-43 may also have a direct pathogenic role in FTLD disorders. ..
  68. Cannon A, Yang B, Knight J, Farnham I, Zhang Y, Wuertzer C, et al. Neuronal sensitivity to TDP-43 overexpression is dependent on timing of induction. Acta Neuropathol. 2012;123:807-23 pubmed publisher
    ..Finally, our adult induction of hTDP-43 strategy provides a mouse model that develops critical pathological features that are directly relevant for human TDP-43 proteinopathies. ..
  69. Fuentealba R, Udan M, Bell S, Wegorzewska I, Shao J, Diamond M, et al. Interaction with polyglutamine aggregates reveals a Q/N-rich domain in TDP-43. J Biol Chem. 2010;285:26304-14 pubmed publisher
  70. Furukawa Y, Kaneko K, Nukina N. Molecular properties of TAR DNA binding protein-43 fragments are dependent upon its cleavage site. Biochim Biophys Acta. 2011;1812:1577-83 pubmed publisher
    ..Molecular properties of TDP-43 fragments thus significantly depend upon its cleavage site, which might reflect distinct molecular pathologies among sub-types of TDP-43 proteinopathies. ..
  71. Neumann M, Sampathu D, Kwong L, Truax A, Micsenyi M, Chou T, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130-3 pubmed
    ..TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders. ..
  72. Kasai T, Tokuda T, Ishigami N, Sasayama H, Foulds P, Mitchell D, et al. Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neuropathol. 2009;117:55-62 pubmed publisher
    ..Raised TDP-43 levels in the CSF may preempt the formation of TDP-43 pathology in the central nervous system, or correlate with early-stage TDP-43 pathology, and accordingly be a biomarker for the early stage of ALS. ..
  73. Kim S, Shi Y, Hanson K, Williams L, Sakasai R, Bowler M, et al. Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1. J Biol Chem. 2009;284:8083-92 pubmed publisher
    ..Our findings suggest that UBQLN is a polyubiquitin-TDP-43 cochaperone that mediates the autophagosomal delivery and/or proteasome targeting of TDP-43 aggregates. ..
  74. Gitcho M, Strider J, Carter D, Taylor Reinwald L, Forman M, Goate A, et al. VCP mutations causing frontotemporal lobar degeneration disrupt localization of TDP-43 and induce cell death. J Biol Chem. 2009;284:12384-98 pubmed publisher
    ..These results suggest that VCP mutation-induced neurodegeneration is mediated by several mechanisms. ..
  75. Volkening K, Leystra Lantz C, Yang W, Jaffee H, Strong M. 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. 2009;1305:168-82 pubmed publisher
    ..These data suggest that NFL mRNA processing is fundamentally altered in ALS spinal motor neurons to favour compartmentalization within both stress granules and P-bodies, and that TDP-43 plays a fundamental role in this process. ..
  76. Elden A, Kim H, Hart M, Chen Plotkin A, Johnson B, Fang X, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010;466:1069-75 pubmed publisher
    ..Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies. ..
  77. Zhang T, Mullane P, Periz G, Wang J. TDP-43 neurotoxicity and protein aggregation modulated by heat shock factor and insulin/IGF-1 signaling. Hum Mol Genet. 2011;20:1952-65 pubmed publisher
    ..elegans and mammalian cells. These results suggest that protein misfolding underlies the aging-dependent neurodegeneration associated with TDP-43 and that the insulin/IGF-1 signaling may be a target for therapies. ..
  78. Rothstein J. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol. 2009;65 Suppl 1:S3-9 pubmed publisher
    ..Convergence of these pathways is likely to mediate disease onset and progression. ..
  79. Schwab C, Arai T, Hasegawa M, Yu S, McGeer P. Colocalization of transactivation-responsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease. J Neuropathol Exp Neurol. 2008;67:1159-65 pubmed publisher
    ..Our results further add to the hypothesis that TDP-43 may be involved in the pathology of a variety of neurodegenerative disorders. ..
  80. Ling S, Albuquerque C, Han J, Lagier Tourenne C, Tokunaga S, Zhou H, et al. ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci U S A. 2010;107:13318-23 pubmed publisher
    ..Taken together, abnormal stability of mutant TDP-43 and its enhanced binding to normal FUS/TLS imply a convergence of pathogenic pathways from mutant TDP-43 and FUS/TLS in ALS. ..
  81. Brady O, Meng P, Zheng Y, Mao Y, Hu F. Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1. J Neurochem. 2011;116:248-59 pubmed publisher
    ..These studies suggest that aggregation of TDP-43 C-terminal fragments is regulated by phosphorylation events and both the autophagy and proteasome-mediated degradation pathways. ..
  82. Fujita Y, Ikeda M, Yanagisawa T, Senoo Y, Okamoto K. Different clinical and neuropathologic phenotypes of familial ALS with A315E TARDBP mutation. Neurology. 2011;77:1427-31 pubmed publisher
    ..The clinical and neuropathologic phenotypes of FALS may differ even with the same mutation of TARDBP, encoding TDP-43. Isolated TDP-43 pathology can produce ALS-plus syndrome. ..
  83. Brettschneider J, Del Tredici K, Irwin D, Grossman M, Robinson J, Toledo J, et al. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol. 2014;127:423-439 pubmed publisher
    ..We interpret the four neuropathological patterns in bvFTD to be consistent with the hypothesis that pTDP-43 pathology can spread sequentially and may propagate along axonal pathways. ..
  84. Scotter E, Vance C, Nishimura A, Lee Y, Chen H, Urwin H, et al. Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species. J Cell Sci. 2014;127:1263-78 pubmed publisher
    ..Therapies for clearing excess TDP-43 should therefore target a combination of these pathways. ..
  85. Kabashi E, Daoud H, Rivière J, Valdmanis P, Valdamanis P, Bourgouin P, et al. No TARDBP mutations in a French Canadian population of patients with Parkinson disease. Arch Neurol. 2009;66:281-2 pubmed publisher
  86. Chiò A, Calvo A, Moglia C, Restagno G, Ossola I, Brunetti M, et al. Amyotrophic lateral sclerosis-frontotemporal lobar dementia in 3 families with p.Ala382Thr TARDBP mutations. Arch Neurol. 2010;67:1002-9 pubmed publisher
    ..Three apparently unrelated families with familial ALS carrying the p.Ala382Thr TARDBP missense mutation developed FTLD. In these families, FTLD cosegregates with ALS. Patients with ALS carrying TARDBP mutations may develop FTLD. ..
  87. Wang J, Brent J, Tomlinson A, Shneider N, McCabe B. The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span. J Clin Invest. 2011;121:4118-26 pubmed publisher
    ..Our results establish that FUS and TDP-43 function together in vivo and suggest that molecular pathways requiring the combined activities of both of these proteins may be disrupted in ALS and FTD. ..
  88. Lee E, Lee V, Trojanowski J. Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat Rev Neurosci. 2011;13:38-50 pubmed publisher
    ..In addition, the distinct possibility of pleotropic or combined effects - in which gains of toxic properties and losses of normal TDP43 functions act together - needs to be considered. ..
  89. Xiao S, Sanelli T, Dib S, Sheps D, Findlater J, Bilbao J, et al. RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS. Mol Cell Neurosci. 2011;47:167-80 pubmed publisher
    ..Of eight genes meeting these criteria, five were differentially spliced in ALS versus control. This supports the premise that abnormalities of TDP-43 in ALS are reflected in changes of RNA processing. ..
  90. Li W, Jin Y, Prazak L, Hammell M, Dubnau J. Transposable elements in TDP-43-mediated neurodegenerative disorders. PLoS ONE. 2012;7:e44099 pubmed publisher
    ..Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases. ..
  91. Buratti E, Brindisi A, Giombi M, Tisminetzky S, Ayala Y, Baralle F. 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;280:37572-84 pubmed
    ..Finally, through splicing complex analysis, we show that splicing inhibition mediated by TDP-43 occurs at the earliest stages of spliceosomal assembly. ..