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Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis
Cyril Jones Jagaraj, Sayanthooran Saravanabavan, Sonam Parakh, Mrithulabashini Jayakumar, Sara Assar Kashani, Sina Shadfar, Prachi M. Mehta, Shashi Gautam et al.. Brain, 2026-03-09
Topic: Brain proteins, microglia and lab models
Here, we show that cofilin is hyper-phosphorylated in human ALS and disease models compared to controls. These findings reveal aberrant cofilin hyperphosphorylation disrupts actin dynamics, triggering TDP-43 pathology and SG recruitment in SALS. Treatment of neuronal cells with the S3A peptide prevented features of TDP-43 pathology and apoptosis compared to control peptides. These findings thus describe a novel pathogenic mechanism producing TDP-43 pathology, applicable to most ALS cases and other neurodegenerative diseases.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Jagaraj, C. J., Saravanabavan, S., Parakh, S., Jayakumar, M., Kashani, S. A., Shadfar, S., et al. (2026). Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis. Brain. https://doi.org/10.1093/brain/awag096
Vancouver
Jagaraj CJ, Saravanabavan S, Parakh S, Jayakumar M, Kashani SA, Shadfar S, et al. Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis. Brain. 2026. doi:10.1093/brain/awag096. PMID: 41804798.
BibTeX
@article{jagaraj2026-41804798,
author = {Jagaraj, Cyril Jones and Saravanabavan, Sayanthooran and Parakh, Sonam and Jayakumar, Mrithulabashini and Kashani, Sara Assar and Shadfar, Sina and Mehta, Prachi M. and Gautam, Shashi and others},
title = {{Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis}},
journal = {Brain},
year = {2026},
doi = {10.1093/brain/awag096},
pmid = {41804798},
url = {https://doi.org/10.1093/brain/awag096}
}
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Key findings
- Here, we show that cofilin is hyper-phosphorylated in human ALS and disease models compared to controls.
- These findings reveal aberrant cofilin hyperphosphorylation disrupts actin dynamics, triggering TDP-43 pathology and SG recruitment in SALS.
- Treatment of neuronal cells with the S3A peptide prevented features of TDP-43 pathology and apoptosis compared to control peptides.
- These findings thus describe a novel pathogenic mechanism producing TDP-43 pathology, applicable to most ALS cases and other neurodegenerative diseases.
Why it matters
This study found that cofilin is hyper-phosphorylated in human ALS and disease models, disrupting actin dynamics and triggering TDP-43 pathology. Treatment with the S3A peptide prevented features of TDP-43 pathology and apoptosis in neuronal cells, but this is early-stage and not yet tested in patients.
Study details
- Evidence strengthLow
How this study scored 43/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 5 / 5 | 2026 — within 1 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.3× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Julie D. Atkin: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | The University of Queensland: institution h-index 1,516 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41804798) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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