Home › Research › Brain tissue and pathology
Compositional Control of Aging Kinetics in TDP-43 Condensates
Nuria H. Espejo, Alejandro Feito, Ignacio Sanchez‐Burgos, Adiran Garaizar, M. M. Conde, Antonio Rey, Eduardo Pedraza, Alejandro Castro et al.. PRX Life, 2025-10-07
Topic: Brain proteins, microglia and lab models
The spontaneous self-assembly of proteins and nucleic acids into biomolecular condensates has been shown to ubiquitously contribute to the functional compartmentalization of the cell. However, their liquid-to-solid transformation (i.e., aging) driven by interprotein β -sheet transitions represents a hallmark of multiple neurodegenerative disorders. We perform molecular dynamics simulations to elucidate the role of different biomolecules in regulating the aging kinetics of TDP-43, an RNA-binding protein linked to amyotrophic lateral sclerosis and frontotemporal dementia. We find that while arginine-rich peptides accelerate the nucleation of interprotein β -sheet structures, the inclusion of RNAs and the HSP70 chaperone slows down their emergence. Interestingly, we observe a correlation between the protein compactness—governed by the condensate composition—and aging kinetics. Moreover, we find that near-interfacial regions of TDP-43 condensates exhibit faster interprotein transitions than the core of the condensate. Together, our findings underscore the major role of client biomolecules in controlling the propensity of multicomponent condensates to form harmful solidlike states.
Key findings
- Together, our findings underscore the major role of client biomolecules in controlling the propensity of multicomponent condensates to form harmful solidlike states.
Why it matters
In molecular dynamics simulations, arginine-rich peptides accelerated the formation of harmful β-sheet structures in TDP-43 condensates, while RNAs and the HSP70 chaperone slowed it down. These are computer simulation findings about condensate aging, not a treatment tested in people.
Study details
- Evidence strengthLow
How this study scored 39/100
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 (PRX Life) |
| Journal's citation record | 0 / 4 | PRX Life: journal h-index 18 (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 | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jorge R. Espinosa: h-index 40 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 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).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Espejo, N. H., Feito, A., Sanchez‐Burgos, I., Garaizar, A., Conde, M. M., Rey, A., et al. (2025). Compositional Control of Aging Kinetics in TDP-43 Condensates. PRX Life. https://doi.org/10.1103/w7g3-6rsd
Vancouver
Espejo NH, Feito A, Sanchez‐Burgos I, Garaizar A, Conde MM, Rey A, et al. Compositional Control of Aging Kinetics in TDP-43 Condensates. PRX Life. 2025. doi:10.1103/w7g3-6rsd.
BibTeX
@article{espejo2025-561ddaf5,
author = {Espejo, Nuria H. and Feito, Alejandro and Sanchez‐Burgos, Ignacio and Garaizar, Adiran and Conde, M. M. and Rey, Antonio and Pedraza, Eduardo and Castro, Alejandro and others},
title = {{Compositional Control of Aging Kinetics in TDP-43 Condensates}},
journal = {PRX Life},
year = {2025},
doi = {10.1103/w7g3-6rsd},
url = {https://doi.org/10.1103/w7g3-6rsd}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 17.
Related studies in Brain tissue and pathology
Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; 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.