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Non-coding RNA in C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction
Douglas AGL.. Non-coding RNA research, 2018-09-10
Topic: Brain proteins, microglia and lab models
A hexanucleotide repeat expansion in the first intron/promoter region of C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both sense and antisense transcripts exist at the C9orf72 locus but the function of the antisense lncRNA is unknown. RNA toxicity of the transcribed repeat expansion has been implicated in the pathogenesis of C9orf72 -related ALS/FTD, not only through direct sequestration of important RNA binding proteins but also indirectly through non-ATG dependent translation into dipeptide repeats. Formation of RNA/DNA hybrid R-loops may also play a key role in the pathogenesis of this condition and this mechanism could provide a link between the repeat expansion, DNA damage, repeat instability and deficiency of RNA binding proteins. Non-coding C9orf72 antisense transcripts could also act to epigenetically regulate gene expression at the locus. The potential effects of such non-coding RNAs should be considered in the design of antisense oligonucleotide therapeutics for C9orf72 -related ALS/FTD. Furthermore, the mechanisms of RNA dysregulation exemplified by C9orf72 -related disease may help illustrate more broadly how a "perfect storm" of dysfunction occurs in ALS/FTD and how targeting these factors could lead to corrective or preventative therapies.
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APA 7th
Douglas, A. G. L. (2018). Non-coding RNA in C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction. Non-coding RNA research. https://doi.org/10.1016/j.ncrna.2018.09.001
Vancouver
Douglas AGL. Non-coding RNA in C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction. Non-coding RNA research. 2018. doi:10.1016/j.ncrna.2018.09.001. PMID: 30533567.
BibTeX
@article{douglas2018-30533567,
author = {Douglas, A. G. L.},
title = {{Non-coding RNA in C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction}},
journal = {Non-coding RNA research},
year = {2018},
doi = {10.1016/j.ncrna.2018.09.001},
pmid = {30533567},
url = {https://doi.org/10.1016/j.ncrna.2018.09.001}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- RNA toxicity of the transcribed repeat expansion has been implicated in the pathogenesis of C9orf72 -related ALS/FTD, not only through direct sequestration of important RNA binding proteins but also indirectly through non-ATG dependent translation into dipeptide repeats.
- Formation of RNA/DNA hybrid R-loops may also play a key role in the pathogenesis of this condition and this mechanism could provide a link between the repeat expansion, DNA damage, repeat instability and deficiency of RNA binding proteins.
- Non-coding C9orf72 antisense transcripts could also act to epigenetically regulate gene expression at the locus.
- The potential effects of such non-coding RNAs should be considered in the design of antisense oligonucleotide therapeutics for C9orf72 -related ALS/FTD.
- Furthermore, the mechanisms of RNA dysregulation exemplified by C9orf72 -related disease may help illustrate more broadly how a "perfect storm" of dysfunction occurs in ALS/FTD and how targeting these factors could lead to corrective or preventative therapies.
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Study details
- Evidence strengthLow
How this study scored 41/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Non-coding RNA research) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30533567) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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