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β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing
Yi Hu, Pascal Kienlen-Campard, Tzu-Chun Tang, Florian Perrin, Rémi Opsomer, Marie Decock, Xiaoshu Pan, Jean-Noel Octave et al.. Scientific reports, 2017-12-07
Topic: Disease mechanisms in lab and animal studies
Familial mutations in C99 can increase the total level of the soluble Aβ peptides produced by proteolysis, as well as the Aβ42/Aβ40 ratio, both of which are linked to the progression of Alzheimer's disease. We show that the extracellular sequence of C99 forms β-sheet structure upon interaction with membrane bilayers. Mutations that disrupt this structure result in a significant increase in Aβ production and, in specific cases, result in an increase in the amount of Aβ42 relative to Aβ40. Fourier transform infrared and solid-state NMR spectroscopic studies reveal a central β-hairpin within the extracellular sequence comprising Y10-E11-V12 and L17-V18-F19 connected by a loop involving H13-H14-Q15. These results suggest how familial mutations in the extracellular sequence influence C99 processing and provide a structural basis for the development of small molecule modulators that would reduce Aβ production.
Key findings
- Mutations that disrupt this structure result in a significant increase in Aβ production and, in specific cases, result in an increase in the amount of Aβ42 relative to Aβ40.
- These results suggest how familial mutations in the extracellular sequence influence C99 processing and provide a structural basis for the development of small molecule modulators that would reduce Aβ production.
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Study details
- Evidence strengthLow
How this study scored 39/100
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, multi-centre collaboration and free to read, so those were left out: it earned 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Scientific reports) |
| 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 | 2017 — 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 29215043) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
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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
Hu, Y., Kienlen-Campard, P., Tang, T.-C., Perrin, F., Opsomer, R., Decock, M., et al. (2017). β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing. Scientific reports. https://doi.org/10.1038/s41598-017-17144-0
Vancouver
Hu Y, Kienlen-Campard P, Tang T.-C, Perrin F, Opsomer R, Decock M, et al. β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing. Scientific reports. 2017. doi:10.1038/s41598-017-17144-0. PMID: 29215043.
BibTeX
@article{hu2017-29215043,
author = {Hu, Yi and Kienlen-Campard, Pascal and Tang, Tzu-Chun and Perrin, Florian and Opsomer, Rémi and Decock, Marie and Pan, Xiaoshu and Octave, Jean-Noel and others},
title = {{β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing}},
journal = {Scientific reports},
year = {2017},
doi = {10.1038/s41598-017-17144-0},
pmid = {29215043},
url = {https://doi.org/10.1038/s41598-017-17144-0}
}
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