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DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay
Yingzhi Ye, Zhe Zhang, Yu Xiao, Chengzhang Zhu, Noelle Wright, Julie Asbury, Yongxin Huang, Wei J. Wang et al.. Neuron, 2026-03-09
Topic: Brain proteins, microglia and lab models
The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping scavenger enzyme (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal that TDP-43 LOF leads to aberrant mRNA degradation via dysregulating the properties and activity of processing bodies (P-bodies). TDP-43 interacts with P-body component proteins, potentially influencing their dynamic equilibrium and assembly into ribonucleoprotein (RNP) granules. Loss of TDP-43 hyperactivates P-bodies, increasing mRNA association and RNA decay. Reducing DCPS restores P-body integrity and RNA turnover, ultimately improving neuronal survival. Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.
Key findings
- Our findings reveal that TDP-43 LOF leads to aberrant mRNA degradation via dysregulating the properties and activity of processing bodies (P-bodies).
- Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.
Why it matters
Using CRISPR interference screening in human neurons, this study identified DCPS as a genetic modifier of TDP-43 loss-of-function neurotoxicity, showing that loss of TDP-43 hyperactivates P-bodies and increases mRNA decay, and that reducing DCPS improves neuronal survival. It identifies DCPS as a potential therapeutic target but these are laboratory findings with no treatment, cure or prevention tested in patients.
Study details
- Evidence strengthLow
How this study scored 45/100
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 (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (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 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 12.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Shuying Sun: h-index 32 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41943580) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 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
Ye, Y., Zhang, Z., Xiao, Y., Zhu, C., Wright, N., Asbury, J., et al. (2026). DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay. Neuron. https://doi.org/10.1016/j.neuron.2026.01.018
Vancouver
Ye Y, Zhang Z, Xiao Y, Zhu C, Wright N, Asbury J, et al. DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay. Neuron. 2026. doi:10.1016/j.neuron.2026.01.018. PMID: 41943580.
BibTeX
@article{ye2026-41943580,
author = {Ye, Yingzhi and Zhang, Zhe and Xiao, Yu and Zhu, Chengzhang and Wright, Noelle and Asbury, Julie and Huang, Yongxin and Wang, Wei J. and others},
title = {{DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay}},
journal = {Neuron},
year = {2026},
doi = {10.1016/j.neuron.2026.01.018},
pmid = {41943580},
url = {https://doi.org/10.1016/j.neuron.2026.01.018}
}
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