The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Differential roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of soluble and aggregated TDP-43 species
Open accessAbstract
TARDBP (TDP-43) is the major pathological protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Large TDP-43 aggregates decorated by degradation adaptor proteins are seen in the cytoplasm of remaining neurons in patients post mortem. TDP-43 accumulation, and ALS-linked mutations within degradation pathways, implicates failed TDP-43 clearance as a primary disease mechanism. Here we report the differential roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of TDP-43. We have investigated the effects of UPS and autophagy inhibitors on the degradation, localisation and mobility of soluble and insoluble TDP-43. We find that soluble TDP-43 is degraded primarily by the UPS, while aggregated TDP-43 clearance requires autophagy. Cellular macroaggregates, which recapitulate many pathological features of patient aggregates, are reversible when both the UPS and autophagy are competent. Their clearance involves the autophagic removal of oligomeric TDP-43. We speculate that in addition to age-related decline, a second hit in the UPS or autophagy pathways drives the accumulation of TDP-43 in ALS and FTD. Therapies for clearing excess TDP-43 should therefore be targeted to a combination of these pathways.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,221
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y.-J., Jiang, Q., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,304
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Ubiquitinated 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
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 1×
“Published half- lives for the endogenous TDP-43 transcript in various cell types range from 1.9 h to 10.3 h (Ayala et al., 2011; Schwanhäusser et al., 2011; Sharova et al., 2009).”
BackgroundInfluentialCui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, K., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,203
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · cited 3×
“, 2004) and acts to recruit LC3-positive autophagosomes (Pankiv et al., 2007).”
BackgroundMethod
Cited by
The mechanisms and roles of selective autophagy in mammals
Vargas, J. N. S., Hamasaki, M., Kawabata, T., Youle, R. J., & Yoshimori, T. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00542-2 · Cited by 1,016
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Cirulli, E. T., Lasseigne, B. N., Petrovski, S., Sapp, P. C., Dion, P. A., Leblond, C. S., Couthouis, J., Lu, Y.-F., Wang, Q., Krueger, B. J., et al. (2015) · Science · doi:10.1126/science.aaa3650 · Cited by 966
Self-citationMolecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis
Prasad, A., Bharathi, V., Sivalingam, V., Girdhar, A., & Patel, B. K. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00025 · Cited by 774
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
TDP-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
Self-citation
Metadata
- Authors
- Scotter, E. L., Vance, C., Nishimura, A. L., Lee, Y.-B., Chen, H.-J., Urwin, H., Sardone, V., Mitchell, J. C., Rogelj, B., Rubinsztein, D. C., & Shaw, C. E.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- Volume
- 127
- Issue
- Pt 6
- Pages
- 1263-78
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1965376857
- Cited by
- 268
- References
- 77
- FWCI
- 14.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Differential roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of soluble and aggregated TDP-43 species. https://app.cochat.ai/papers/10.1242/jcs.140087
- The paper
- Scotter, E. L., Vance, C., Nishimura, A. L., Lee, Y.-B., Chen, H.-J., Urwin, H., Sardone, V., Mitchell, J. C., Rogelj, B., Rubinsztein, D. C., & Shaw, C. E. (2014). Differential roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of soluble and aggregated TDP-43 species. Journal of Cell Science. https://doi.org/10.1242/jcs.140087
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
