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C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins
Zhang YJ, Gendron TF, Grima JC, Sasaguri H, Jansen-West K, Xu YF, Katzman RB, Gass J et al.. Nature neuroscience, 2016-03-21
Topic: Brain proteins, microglia and lab models
Neuronal inclusions of poly(GA), a protein unconventionally translated from G4C2 repeat expansions in C9ORF72, are abundant in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) caused by this mutation. To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS. These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation.
Key findings
- To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS.
- These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation.
- HR23 proteins involved in proteasomal degradation and proteins involved in nucleocytoplasmic transport were sequestered by poly(GA) in these mice.
- HR23A and HR23B similarly colocalized to poly(GA) inclusions in C9ORF72 expansion carriers.
Why it matters
In this mouse study, animals with poly(GA) pathology showed neurodegeneration and behavioral abnormalities resembling frontotemporal dementia and ALS, and the poly(GA) clumps trapped HR23 and nucleocytoplasmic transport proteins. This is animal research on C9ORF72-related disease, not Alzheimer's disease, and does not test any treatment, cure, or prevention for Alzheimer's.
Study details
- Evidence strengthLow
How this study scored 58/100
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 (Nature neuroscience) |
| Journal's citation record | 4 / 4 | Nature Neuroscience: journal h-index 593 (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 | 1 / 5 | 2016 — within 20 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 | 6 / 7 | Cited 316 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.3 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 5 / 6 | Cited 26.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Leonard Petrucelli: h-index 112 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26998601) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Zhang, Y. J., Gendron, T. F., Grima, J. C., Sasaguri, H., Jansen-West, K., Xu, Y. F., et al. (2016). C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nature neuroscience. https://doi.org/10.1038/nn.4272
Vancouver
Zhang YJ, Gendron TF, Grima JC, Sasaguri H, Jansen-West K, Xu YF, et al. C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nature neuroscience. 2016. doi:10.1038/nn.4272. PMID: 26998601.
BibTeX
@article{zhang2016-26998601,
author = {Zhang, Y. J. and Gendron, T. F. and Grima, J. C. and Sasaguri, H. and Jansen-West, K. and Xu, Y. F. and Katzman, R. B. and Gass, J. and others},
title = {{C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins}},
journal = {Nature neuroscience},
year = {2016},
doi = {10.1038/nn.4272},
pmid = {26998601},
url = {https://doi.org/10.1038/nn.4272}
}
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