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Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex
Tolia A, Chávez-Gutiérrez L, De Strooper B.. The Journal of biological chemistry, 2006-07-14
Topic: Brain proteins, microglia and lab models
Gamma-secretase is a multiprotein complex responsible for the intramembranous cleavage of the amyloid precursor protein and other type I transmembrane proteins. Mutations in Presenilin, the catalytic core of this complex, cause Alzheimer disease. Little is known about the structure of the protein and even less about the catalytic mechanism, which involves proteolytic cleavage in the hydrophobic environment of the cell membrane.
Key findings
- Mutations in Presenilin, the catalytic core of this complex, cause Alzheimer disease.
- Little is known about the structure of the protein and even less about the catalytic mechanism, which involves proteolytic cleavage in the hydrophobic environment of the cell membrane.
- It is basically unclear how water, needed to perform hydrolysis, is provided to this reaction.
- Presenilin transmembrane domains 6 and 7 seem critical in this regard, as each bears a critical aspartate contributing to catalytic activity.
Why it matters
This laboratory work examines how parts of presenilin may form a water-containing cavity needed for γ-secretase to cut proteins inside the membrane. It is basic structural research and does not show any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 1 / 5 | 2006 — older than 20 years, still counted |
| 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 | 5 / 7 | Cited 134 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.1 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 4 / 6 | Cited 9.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bart De Strooper: h-index 146 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | KU Leuven: institution h-index 1,386 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16844686) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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Read the original
- DOI: 10.1074/jbc.m604997200
- PubMed: 16844686
- Original source →
- Free full text: Journal of Biological Chemistry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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. Check the citation against the original before you use it.
APA 7th
Tolia, A., Chávez-Gutiérrez, L., & De Strooper, B. (2006). Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m604997200
Vancouver
Tolia A, Chávez-Gutiérrez L, De Strooper B. Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex. The Journal of biological chemistry. 2006. doi:10.1074/jbc.m604997200. PMID: 16844686.
BibTeX
@article{tolia2006-16844686,
author = {Tolia, A. and Chávez-Gutiérrez, L. and De Strooper, B.},
title = {{Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex}},
journal = {The Journal of biological chemistry},
year = {2006},
doi = {10.1074/jbc.m604997200},
pmid = {16844686},
url = {https://doi.org/10.1074/jbc.m604997200}
}
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