Evidence map›Paper›PMID 28510586›Full record

ArticlePloS one2017

Truncation of the TAR DNA-binding protein 43 is not a prerequisite for cytoplasmic relocalization, and is suppressed by caspase inhibition and by introduction of the A90V sequence variant.

Heike J Wobst, Louise Delsing, Nicholas J Brandon, Stephen J Moss

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43Frontiers in cell and developmental biology · 2023
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
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  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Heike J WobstAstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, MA, United States of America.
Louise DelsingAstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, MA, United States of America.
Nicholas J BrandonAstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, MA, United States of America.
Stephen J MossAstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, MA, United States of America.
Tufts University · USAstraZeneca (Sweden) · SEAstraZeneca (United States) · US

Funding

Constructing inhibitory synapsesR01NS051195 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI MOSS, STEPHEN J · 2006 to 2014
$3.2M
Novel actions of neurosteroids on GABA (A) receptor traffickingR01MH097446 · NIMH · TUFTS UNIVERSITY BOSTON · PI DAVIES, PAUL ANDREW, MOSS, STEPHEN J · 2013 to 2017
$2.1M
Deficits in KCC2 activity and the pathophysiology of Status EpilepticusR01NS087662 · NINDS · TUFTS UNIVERSITY BOSTON · PI MOSS, STEPHEN J · 2014 to 2018
$2.0M
The role of ubiquitination in regulating GABA(A) receptor functional expressionR01NS056359 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI MOSS, STEPHEN J · 2007 to 2010
$1.4M
Deficits in KCC2 activity and the pathophysiology of Autism spectrum disordersR21MH106954 · NIMH · TUFTS UNIVERSITY BOSTON · PI MOSS, STEPHEN J · 2015 to 2016
$454k
Impaired KCC2 function underlies pharmacoresistant seizuresR21NS080064 · NINDS · TUFTS UNIVERSITY BOSTON · PI MOSS, STEPHEN J · 2013 to 2014
$452k
NIMH NIH HHS R01 MH097446NIMH NIH HHS R21 MH106954NINDS NIH HHS R01 NS051195NINDS NIH HHS R01 NS056359NINDS NIH HHS R01 NS087662NINDS NIH HHS R21 NS080064
6 · The paper itself

Abstract

The RNA-binding and -processing protein TAR DNA-binding protein 43 (TDP-43) is heavily linked to the underlying causes and pathology of neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. In these diseases, TDP-43 is mislocalized, hyperphosphorylated, ubiquitinated, aggregated and cleaved. The importance of TDP-43 cleavage in the disease pathogenesis is still poorly understood. Here we detail the use of D-sorbitol as an exogenous stressor that causes TDP-43 cleavage in HeLa cells, resulting in a 35 kDa truncated product that accumulates in the cytoplasm within one hour of treatment. We confirm that the formation of this 35 kDa cleavage product is mediated by the activation of caspases. Inhibition of caspases blocks the cleavage of TDP-43, but does not prevent the accumulation of full-length protein in the cytoplasm. Using D-sorbitol as a stressor and caspase activator, we also demonstrate that the A90V variant of TDP-43, which lies adjacent to the caspase cleavage site within the nuclear localization sequence of TDP-43, confers partial resistance against caspase-mediated generation of the 35 kDa cleavage product.

Indexed as

CodonGenetic VariationAmino Acid SubstitutionCaspasesCytoplasmDNA-Binding ProteinsHeLa CellsHumansMutationOsmotic PressureOxidative StressProtein BindingProtein Interaction Domains and MotifsProtein TransportProteolysisSorbitolCaspasesCodonDNA-Binding ProteinsSorbitolTARDBP protein, human

Identifiers

PMID28510586
PMCPMC5433705
OpenAlexW2614705539

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.