Home › Research › Brain tissue and pathology
SUMO2/3 conjugation of TDP-43 protects against aggregation
Enza Maria Verde, Francesco Antoniani, Laura Mediani, Valentina Secco, Samuele Crotti, Maria Celidea Ferrara, Jonathan Vinet, Aleksandra V. Sergeeva et al.. Science Advances, 2025-02-21
Topic: Brain proteins, microglia and lab models
Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding protein 43) is a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, TDP-43 becomes SUMO2/3-ylated by the SUMO E3 ligase protein PIAS4 (protein inhibitor of activated STAT 4) and enriches in cytoplasmic stress granules (SGs). Upon pharmacological inhibition of TDP-43 SUMO2/3-ylation or PIAS4 depletion, TDP-43 enrichment in SGs is accompanied by irreversible aggregation. In cells that are unable to assemble SGs, SUMO2/3-ylation of TDP-43 is strongly impaired, supporting the notion that SGs are compartments that promote TDP-43 SUMO2/3-ylation during oxidative stress. Binding of TDP-43 to UG-rich RNA antagonizes PIAS4-mediated SUMO2/3-ylation, while RNA dissociation promotes TDP-43 SUMO2/3-ylation. We conclude that SUMO2/3 protein conjugation is a cellular mechanism to stabilize cytosolic RNA-free TDP-43 against aggregation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Verde, E. M., Antoniani, F., Mediani, L., Secco, V., Crotti, S., Ferrara, M. C., et al. (2025). SUMO2/3 conjugation of TDP-43 protects against aggregation. Science Advances. https://doi.org/10.1126/sciadv.adq2475
Vancouver
Verde EM, Antoniani F, Mediani L, Secco V, Crotti S, Ferrara MC, et al. SUMO2/3 conjugation of TDP-43 protects against aggregation. Science Advances. 2025. doi:10.1126/sciadv.adq2475. PMID: 39982984.
BibTeX
@article{verde2025-39982984,
author = {Verde, Enza Maria and Antoniani, Francesco and Mediani, Laura and Secco, Valentina and Crotti, Samuele and Ferrara, Maria Celidea and Vinet, Jonathan and Sergeeva, Aleksandra V. and others},
title = {{SUMO2/3 conjugation of TDP-43 protects against aggregation}},
journal = {Science Advances},
year = {2025},
doi = {10.1126/sciadv.adq2475},
pmid = {39982984},
url = {https://doi.org/10.1126/sciadv.adq2475}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- We conclude that SUMO2/3 protein conjugation is a cellular mechanism to stabilize cytosolic RNA-free TDP-43 against aggregation.
Why it matters
In cell experiments, this study found that SUMO2/3 conjugation of TDP-43 helps stabilize the protein against irreversible aggregation during oxidative stress. This is an early laboratory finding about a possible protective mechanism, not a treatment tested in people.
Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science Advances) |
| Journal's citation record | 3 / 4 | Science Advances: journal h-index 378 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 29 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 16.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Serena Carra: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,511 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39982984) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 15.
Later studies that cite this one
4 studies in the alzhub library list this one in their references.
Related studies in Brain tissue and pathology
Also tagged “tdp-43”
1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.