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C9orf72-mediated ALS and FTD: multiple pathways to disease
Balendra R, Isaacs AM.. Nature reviews. Neurology, 2018-09-01
Topic: Brain proteins, microglia and lab models
The discovery that repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has revolutionized our understanding of these diseases. Substantial headway has been made in characterizing C9orf72-mediated disease and unravelling its underlying aetiopathogenesis. Three main disease mechanisms have been proposed: loss of function of the C9orf72 protein and toxic gain of function from C9orf72 repeat RNA or from dipeptide repeat proteins produced by repeat-associated non-ATG translation. Several downstream processes across a range of cellular functions have also been implicated. In this article, we review the pathological and mechanistic features of C9orf72-associated FTD and ALS (collectively termed C9FTD/ALS), the model systems used to study these conditions, and the probable initiators of downstream disease mechanisms. We suggest that a combination of upstream mechanisms involving both loss and gain of function and downstream cellular pathways involving both cell-autonomous and non-cell-autonomous effects contributes to disease progression.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Balendra, R., & Isaacs, A. M. (2018). C9orf72-mediated ALS and FTD: multiple pathways to disease. Nature reviews. Neurology. https://doi.org/10.1038/s41582-018-0047-2
Vancouver
Balendra R, Isaacs AM. C9orf72-mediated ALS and FTD: multiple pathways to disease. Nature reviews. Neurology. 2018. doi:10.1038/s41582-018-0047-2. PMID: 30120348.
BibTeX
@article{balendra2018-30120348,
author = {Balendra, R. and Isaacs, A. M.},
title = {{C9orf72-mediated ALS and FTD: multiple pathways to disease}},
journal = {Nature reviews. Neurology},
year = {2018},
doi = {10.1038/s41582-018-0047-2},
pmid = {30120348},
url = {https://doi.org/10.1038/s41582-018-0047-2}
}
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Key findings
- We suggest that a combination of upstream mechanisms involving both loss and gain of function and downstream cellular pathways involving both cell-autonomous and non-cell-autonomous effects contributes to disease progression.
Why it matters
This review proposes that C9orf72-related ALS and FTD arise from a combination of loss and gain of function plus downstream cellular pathways. It is a summary of mechanisms, not a trial, and suggests no specific treatment.
Study details
- Evidence strengthLow
How this study scored 52/100
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 (Nature reviews. Neurology) |
| Journal's citation record | 3 / 4 | Nature Reviews Neurology: journal h-index 269 (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 | 2 / 5 | 2018 — within 10 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 723 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 72.3 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 14.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 4 / 4 | Cited 244 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Adrian M. Isaacs: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30120348) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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