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TDP-43: [GU]-ardian of the transcriptome
Irika R. Sinha, Abigail L. Atkinson, Katherine E. Irwin, Jonathan P. Ling, Philip C. Wong. Molecular Neurodegeneration, 2026-05-14
Topic: Brain proteins, microglia and lab models
TDP-43 is a ubiquitously expressed, primarily nuclear DNA/RNA-binding protein implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). In this review, we examine the structure and regulation of TDP-43, how these features influence its localization and functional activity, and how their disruption may contribute to disease. Among TDP-43's diverse functions, splicing repression of nonconserved RNA sequences termed cryptic exons has emerged as especially central to human disease. TDP-43 nuclear depletion and cytoplasmic aggregation are well-established pathological features in affected neurons and glia of neurodegenerative diseases, and accumulating evidence suggests that loss of TDP-43-mediated splicing repression occurs presymptomatically in disease. Advances in RNA-sequencing have enabled systematic identification of cryptic exon inclusion as a sensitive marker of TDP-43 dysfunction. Here, we synthesize current knowledge of TDP-43 biology and curate datasets from human tissues and experimental models, focusing on cryptic splicing to provide a resource for leveraging cryptic exon biology to better understand, detect, and target TDP-43 dysfunction.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Sinha, I. R., Atkinson, A. L., Irwin, K. E., Ling, J. P., & Wong, P. C. (2026). TDP-43: [GU]-ardian of the transcriptome. Molecular Neurodegeneration. https://doi.org/10.1186/s13024-026-00944-2
Vancouver
Sinha IR, Atkinson AL, Irwin KE, Ling JP, Wong PC. TDP-43: [GU]-ardian of the transcriptome. Molecular Neurodegeneration. 2026. doi:10.1186/s13024-026-00944-2. PMID: 42135847.
BibTeX
@article{sinha2026-42135847,
author = {Sinha, Irika R. and Atkinson, Abigail L. and Irwin, Katherine E. and Ling, Jonathan P. and Wong, Philip C.},
title = {{TDP-43: [GU]-ardian of the transcriptome}},
journal = {Molecular Neurodegeneration},
year = {2026},
doi = {10.1186/s13024-026-00944-2},
pmid = {42135847},
url = {https://doi.org/10.1186/s13024-026-00944-2}
}
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Key findings
- TDP-43 nuclear depletion and cytoplasmic aggregation are well-established pathological features in affected neurons and glia of neurodegenerative diseases, and accumulating evidence suggests that loss of TDP-43-mediated splicing repression occurs presymptomatically in disease.
Why it matters
This review describes how loss of TDP-43's normal role in blocking cryptic exon splicing occurs before symptoms appear in diseases including ALS, FTD, and Alzheimer's disease. It presents cryptic exon inclusion as a sensitive marker of TDP-43 dysfunction that could help detect and target this problem.
Study details
- Evidence strengthLow
How this study scored 42/100
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 (Molecular Neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (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 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 8.7× 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 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Philip C. Wong: h-index 71 (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 42135847) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-026-00944-2
- PubMed: 42135847
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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