The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo
Abstract
TDP-43 has been found in inclusion bodies of multiple neurological disorders, including amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease and Alzheimer's disease. Mutations in the TDP-43 encoding gene, TARDBP, have been subsequently reported in sporadic and familial ALS patients. In order to investigate the pathogenic nature of these mutants, the effects of three consistently reported TARDBP mutations (A315T, G348C and A382T) were tested in cell lines, primary cultured motor neurons and living zebrafish embryos. Each of the three mutants and wild-type (WT) human TDP-43 localized to nuclei when expressed in COS1 and Neuro2A cells by transient transfection. However, when expressed in motor neurons from dissociated spinal cord cultures these mutant TARDBP alleles, but less so for WT TARDBP, were neurotoxic, concomitant with perinuclear localization and aggregation of TDP-43. Finally, overexpression of mutant, but less so of WT, human TARDBP caused a motor phenotype in zebrafish (Danio rerio) embryos consisting of shorter motor neuronal axons, premature and excessive branching as well as swimming deficits. Interestingly, knock-down of zebrafisfh tardbp led to a similar phenotype, which was rescued by co-expressing WT but not mutant human TARDBP. Together these approaches showed that TARDBP mutations cause motor neuron defects and toxicity, suggesting that both a toxic gain of function as well as a novel loss of function may be involved in the molecular mechanism by which mutant TDP-43 contributes to disease pathogenesis.
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Self-citationUbiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
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TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630
Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., Arnold, S. E., Siderowf, A., Grossman, M., Leverenz, J. B., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0261-2 · Cited by 468
TDP ‐ 43 mutation in familial amyotrophic lateral sclerosis
Yokoseki, A., Shiga, A., Tan, C., Tagawa, A., Kaneko, H., Koyama, A., Eguchi, H., Tsujino, A., Ikeuchi, T., Kakita, A., et al. (2008) · Annals of Neurology · doi:10.1002/ana.21392 · Cited by 373
Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1
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Failure of protein quality control in amyotrophic lateral sclerosis
Kabashi, E., & Durham, H. D. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.06.006 · Cited by 90
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Cited by
TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration
Lagier-Tourenne, C., Polymenidou, M., & Cleveland, D. W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq137 · Cited by 1,021
Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration
Lee, E. B., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3121 · Cited by 659
Sellier, C., Campanari, M., Julie Corbier, C., Gaucherot, A., Kolb‐Cheynel, I., Oulad‐Abdelghani, M., Ruffenach, F., Page, A., Ciura, S., Kabashi, E., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201593350 · Cited by 414
Self-citationTDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and Therapeutic Targets
Scotter, E. L., Chen, H.-J., & Shaw, C. E. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0338-x · Cited by 382
Understanding the role of TDP-43 and FUS/TLS in ALS and beyond
Da Cruz, S., & Cleveland, D. W. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.05.029 · Cited by 351
Metadata
- Authors
- Kabashi, E., Lin, L., Tradewell, M. L., Dion, P. A., Bercier, V., Bourgouin, P., Rochefort, D., Bel Hadj, S., Durham, H. D., Velde, C. V., Rouleau, G. A., & Drapeau, P.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-03
- Volume
- 19
- Issue
- 4
- Pages
- 671-683
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2160475742
- Cited by
- 415
- References
- 8
- FWCI
- 19.69
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kabashi, E., Lin, L., Tradewell, M. L., Dion, P. A., Bercier, V., Bourgouin, P., Rochefort, D., Bel Hadj, S., Durham, H. D., Velde, C. V., Rouleau, G. A., & Drapeau, P. (2010). Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddp534
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