Home › Research › TREM2 and immune genetics
Misframed ubiquitin and impaired protein quality control: an early event in Alzheimer's disease
Gentier RJ, van Leeuwen FW.. Frontiers in molecular neuroscience, 2015-09-02
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Amyloid β (Aβ) plaque formation is a prominent cellular hallmark of Alzheimer's disease (AD). To date, immunization trials in AD patients have not been effective in terms of curing or ameliorating dementia. In addition, γ-secretase inhibitor strategies await clinical improvements in AD. These approaches were based upon the idea that autosomal dominant mutations in amyloid precursor protein (APP) and Presenilin 1 (PS1) genes are predictive for treatment of all AD patients. However most AD patients are of the sporadic form which partly explains the failures to treat this multifactorial disease. The major risk factor for developing sporadic AD (SAD) is aging whereas the Apolipoprotein E polymorphism (ε4 variant) is the most prominent genetic risk factor. Other medium-risk factors such as triggering receptor expressed on myeloid cells 2 (TREM2) and nine low risk factors from Genome Wide Association Studies (GWAS) were associated with AD. Recently, pooled GWAS studies identified protein ubiquitination as one of the key modulators of AD. In addition, a brain site specific strategy was used to compare the proteomes of AD patients by an Ingenuity Pathway Analysis. This strategy revealed numerous proteins that strongly interact with ubiquitin (UBB) signaling, and pointing to a dysfunctional ubiquitin proteasome system (UPS) as a causal factor in AD. We reported that DNA-RNA sequence differences in several genes including ubiquitin do occur in AD, the resulting misframed protein of which accumulates in the neurofibrillary tangles (NFTs). This suggests again a functional link between neurodegeneration of the AD type and loss of protein quality control by the UPS. Progress in this field is discussed and modulating the activity of the UPS opens an attractive avenue of research towards slowing down the development of AD and ameliorating its effects by discovering prime targets for AD therapeutics.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gentier, R. J., & van Leeuwen, F. W. (2015). Misframed ubiquitin and impaired protein quality control: an early event in Alzheimer's disease. Frontiers in molecular neuroscience. https://doi.org/10.3389/fnmol.2015.00047
Vancouver
Gentier RJ, van Leeuwen FW. Misframed ubiquitin and impaired protein quality control: an early event in Alzheimer's disease. Frontiers in molecular neuroscience. 2015. doi:10.3389/fnmol.2015.00047. PMID: 26388726.
BibTeX
@article{gentier2015-26388726,
author = {Gentier, R. J. and van Leeuwen, F. W.},
title = {{Misframed ubiquitin and impaired protein quality control: an early event in Alzheimer's disease}},
journal = {Frontiers in molecular neuroscience},
year = {2015},
doi = {10.3389/fnmol.2015.00047},
pmid = {26388726},
url = {https://doi.org/10.3389/fnmol.2015.00047}
}
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
- Other medium-risk factors such as triggering receptor expressed on myeloid cells 2 (TREM2) and nine low risk factors from Genome Wide Association Studies (GWAS) were associated with AD.
- This strategy revealed numerous proteins that strongly interact with ubiquitin (UBB) signaling, and pointing to a dysfunctional ubiquitin proteasome system (UPS) as a causal factor in AD.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in molecular neuroscience) |
| 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 | 1 / 5 | 2015 — 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26388726) |
| Free to read | 2 / 2 | Free to read |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 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 the library that share something with this one. The line above each title says what.