Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia
Swarup V, Hinz FI, Rexach JE, Noguchi KI, Toyoshiba H, Oda A, Hirai K, Sarkar A et al.. Nature medicine, 2018-12-03
Topic: Brain proteins, microglia and lab models
Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Swarup, V., Hinz, F. I., Rexach, J. E., Noguchi, K. I., Toyoshiba, H., Oda, A., et al. (2019). Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia. Nature medicine. https://doi.org/10.1038/s41591-018-0223-3
Vancouver
Swarup V, Hinz FI, Rexach JE, Noguchi KI, Toyoshiba H, Oda A, et al. Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia. Nature medicine. 2019. doi:10.1038/s41591-018-0223-3. PMID: 30510257.
BibTeX
@article{swarup2019-30510257,
author = {Swarup, V. and Hinz, F. I. and Rexach, J. E. and Noguchi, K. I. and Toyoshiba, H. and Oda, A. and Hirai, K. and Sarkar, A. and others},
title = {{Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia}},
journal = {Nature medicine},
year = {2019},
doi = {10.1038/s41591-018-0223-3},
pmid = {30510257},
url = {https://doi.org/10.1038/s41591-018-0223-3}
}
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.
Key findings
- We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration.
- Our results highlight the utility of an integrative, cross-species network approach to drug discovery.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 47/100
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. 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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| 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 | 2019 — 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 30510257) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Genetics
Also tagged “neurodegenerative”
6 studies in the library carry the topic tag “neurodegenerative”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 6 tagged studies.