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Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio
Uemura K, Lill CM, Li X, Peters JA, Ivanov A, Fan Z, DeStrooper B, Bacskai BJ et al.. PloS one, 2009-11-18
Topic: Brain proteins, microglia and lab models
Background Presenilin 1(PS1) is the catalytic subunit of gamma-secretase, the enzyme responsible for the Abeta C-terminal cleavage site, which results in the production of Abeta peptides of various lengths. Production of longer forms of the Abeta peptide occur in patients with autosomal dominant Alzheimer disease (AD) due to mutations in presenilin. Many modulators of gamma-secretase function have been described.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Uemura, K., Lill, C. M., Li, X., Peters, J. A., Ivanov, A., Fan, Z., et al. (2009). Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PloS one. https://doi.org/10.1371/journal.pone.0007893
Vancouver
Uemura K, Lill CM, Li X, Peters JA, Ivanov A, Fan Z, et al. Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PloS one. 2009. doi:10.1371/journal.pone.0007893. PMID: 19924286.
BibTeX
@article{uemura2009-19924286,
author = {Uemura, K. and Lill, C. M. and Li, X. and Peters, J. A. and Ivanov, A. and Fan, Z. and DeStrooper, B. and Bacskai, B. J. and others},
title = {{Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio}},
journal = {PloS one},
year = {2009},
doi = {10.1371/journal.pone.0007893},
pmid = {19924286},
url = {https://doi.org/10.1371/journal.pone.0007893}
}
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Key findings
- Production of longer forms of the Abeta peptide occur in patients with autosomal dominant Alzheimer disease (AD) due to mutations in presenilin.
- Many modulators of gamma-secretase function have been described.
- We hypothesize that these modulators act by a common mechanism by allosterically modifying the structure of presenilin.
- Methodology/principal findings To test this hypothesis we generated a genetically encoded GFP-PS1-RFP (G-PS1-R) FRET probe that allows monitoring of the conformation of the PS1 molecule in its native environment in live cells.
Why it matters
This laboratory study used a FRET probe to test whether modulators of gamma-secretase act by allosterically changing presenilin structure in relation to the amyloid beta(42/40) ratio. It is basic molecular research and does not test any treatment, cure, or prevention in people.
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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 (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (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 | 2009 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 76 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 5.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 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 | 2 / 4 | Last-listed author Oksana Berezovska: h-index 42 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19924286) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
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