Evidence map›Paper›PMID 40149017›Full record

ArticleMolecular neurodegeneration2025

A stress-dependent TDP-43 SUMOylation program preserves neuronal function.

Terry R Suk, Caroline E Part, Jenny L Zhang, Trina T Nguyen, Meghan M Heer, Alejandro Caballero-Gómez, Veronica S Grybas, Paul M McKeever, Benjamin Nguyen, Tahir Ali and 4 more

Abstract read
In one paragraph

Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Review
  2. Article
  3. TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Article
  5. TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026
    Review
  6. The Role of Stress Granules in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
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

14 authors.

Terry R SukUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Caroline E PartUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Jenny L Zhang *University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Trina T Nguyen *University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Meghan M HeerUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Alejandro Caballero-GómezUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Veronica S GrybasUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Paul M McKeeverTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Benjamin NguyenUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Tahir AliUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Steve M CallaghanUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
John M WoulfeUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Janice RobertsonTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Maxime W C RousseauxUniversity of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada. max.rousseaux@uottawa.ca.ORCID 0000-0002-2737-6193

Funding

CIHR PJT-195691
6 · The paper itself

Abstract

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are overwhelmingly linked to TDP-43 dysfunction. Mutations in TDP-43 are rare, indicating that the progressive accumulation of exogenous factors - such as cellular stressors - converge on TDP-43 to play a key role in disease pathogenesis. Post translational modifications such as SUMOylation play essential roles in response to such exogenous stressors. We therefore set out to understand how SUMOylation may regulate TDP-43 in health and disease. We find that TDP-43 is regulated dynamically via SUMOylation in response to cellular stressors. When this process is blocked in vivo, we note age-dependent TDP-43 pathology and sex-specific behavioral deficits linking TDP-43 SUMOylation with aging and disease. We further find that SUMOylation is correlated with human aging and disease states. Collectively, this work presents TDP-43 SUMOylation as an early physiological response to cellular stress, disruption of which may confer a risk for TDP-43 proteinopathy.

Indexed as

DNA-Binding ProteinsNeuronsStress, PhysiologicalSumoylationAgingAmyotrophic Lateral SclerosisAnimalsFemaleFrontotemporal DementiaHumansMaleMiceTDP-43 ProteinopathiesDNA-Binding ProteinsTARDBP protein, humanTardbp protein, mouseALSFTDMouse ModelPathologyPost Translational ModificationsStressSUMOylationTDP-43

Identifiers

PMID40149017
PMCPMC11951803

What Socratic holds

Textmetadata
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 Socratic graph.