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RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo
Désiré L, Bourdin J, Loiseau N, Peillon H, Picard V, De Oliveira C, Bachelot F, Leblond B et al.. The Journal of biological chemistry, 2005-09-08
Topic: Brain proteins, microglia and lab models
beta-Amyloid peptides (Abeta) that form the senile plaques of Alzheimer disease consist mainly of 40- and 42-amino acid (Abeta 40 and Abeta 42) peptides generated from the cleavage of the amyloid precursor protein (APP). Generation of Abeta involves beta-secretase and gamma-secretase activities and is regulated by membrane trafficking of the proteins involved in Abeta production. Here we describe a new small molecule, EHT 1864, which blocks the Rac1 signaling pathways.
Key findings
- Generation of Abeta involves beta-secretase and gamma-secretase activities and is regulated by membrane trafficking of the proteins involved in Abeta production.
- Here we describe a new small molecule, EHT 1864, which blocks the Rac1 signaling pathways.
- In vitro, EHT 1864 blocks Abeta 40 and Abeta 42 production but does not impact sAPPalpha levels and does not inhibit beta-secretase.
- Rather, EHT 1864 modulates APP processing at the level of gamma-secretase to prevent Abeta 40 and Abeta 42 generation.
Why it matters
The small molecule EHT 1864 blocked Rac1 signalling and reduced amyloid-beta 40 and 42 production in vitro and in vivo by modulating APP processing at gamma-secretase. This is early experimental work and does not show a treatment for patients.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on institution's track record, so that was left out: it earned 40 of the 97 points we could judge it on, which is 41 out of 100.
| 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 | 2005 — 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 | Laboratory or animal study (title names “in vitro”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 135 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.9 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 5.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Fabien Schweighoffer: h-index 25 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16150730) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 40 / 97 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 40 of the 97 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m507913200
- PubMed: 16150730
- 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. 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
Désiré, L., Bourdin, J., Loiseau, N., Peillon, H., Picard, V., De Oliveira, C., et al. (2005). RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m507913200
Vancouver
Désiré L, Bourdin J, Loiseau N, Peillon H, Picard V, De Oliveira C, et al. RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m507913200. PMID: 16150730.
BibTeX
@article{desire2005-16150730,
author = {Désiré, L. and Bourdin, J. and Loiseau, N. and Peillon, H. and Picard, V. and De Oliveira, C. and Bachelot, F. and Leblond, B. and others},
title = {{RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m507913200},
pmid = {16150730},
url = {https://doi.org/10.1074/jbc.m507913200}
}
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