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The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS
Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA et al.. Science (New York, N.Y.), 2013-02-07
Topic: Brain proteins, microglia and lab models
Expansion of a GGGGCC hexanucleotide repeat upstream of the C9orf72 coding region is the most common cause of familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTLD/ALS), but the pathomechanisms involved are unknown. As in other FTLD/ALS variants, characteristic intracellular inclusions of misfolded proteins define C9orf72 pathology, but the core proteins of the majority of inclusions are still unknown. Here, we found that most of these characteristic inclusions contain poly-(Gly-Ala) and, to a lesser extent, poly-(Gly-Pro) and poly-(Gly-Arg) dipeptide-repeat proteins presumably generated by non-ATG-initiated translation from the expanded GGGGCC repeat in three reading frames. These findings directly link the FTLD/ALS-associated genetic mutation to the predominant pathology in patients with C9orf72 hexanucleotide expansion.
Key findings
- Here, we found that most of these characteristic inclusions contain poly-(Gly-Ala) and, to a lesser extent, poly-(Gly-Pro) and poly-(Gly-Arg) dipeptide-repeat proteins presumably generated by non-ATG-initiated translation from the expanded GGGGCC repeat in three reading frames.
- These findings directly link the FTLD/ALS-associated genetic mutation to the predominant pathology in patients with C9orf72 hexanucleotide expansion.
Why it matters
In people with the C9orf72 repeat expansion, the most common inherited cause of frontotemporal lobar degeneration and ALS, the proteins at the core of most brain inclusions were unknown. This study found that most of these inclusions contain abnormal dipeptide-repeat proteins, mainly poly-(Gly-Ala), with less poly-(Gly-Pro) and poly-(Gly-Arg), which the authors say are "presumably" made directly from the expanded repeat. This links the mutation to the main pathology in these patients, but it does not show that the proteins cause the disease, and it is not a study of Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 59/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| Journal's citation record | 4 / 4 | Science: journal h-index 1,754 (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 | 2013 — 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 | 7 / 7 | Cited 1,285 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 85.7 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 6 / 6 | Cited 75.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 49 other studies in this library |
| Still being cited | 3 / 4 | Cited 191 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Dieter Edbauer: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23393093) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 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
Mori, K., Weng, S. M., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., et al. (2013). The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science (New York, N.Y.). https://doi.org/10.1126/science.1232927
Vancouver
Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science (New York, N.Y.). 2013. doi:10.1126/science.1232927. PMID: 23393093.
BibTeX
@article{mori2013-23393093,
author = {Mori, K. and Weng, S. M. and Arzberger, T. and May, S. and Rentzsch, K. and Kremmer, E. and Schmid, B. and Kretzschmar, H. A. and others},
title = {{The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS}},
journal = {Science (New York, N.Y.)},
year = {2013},
doi = {10.1126/science.1232927},
pmid = {23393093},
url = {https://doi.org/10.1126/science.1232927}
}
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