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The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein
Kojro E, Postina R, Buro C, Meiringer C, Gehrig-Burger K, Fahrenholz F.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2006-01-09
Topic: Brain proteins, microglia and lab models
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has neurotrophic as well as anti-apoptotic properties and is involved in learning and memory processes. Its specific G protein-coupled receptor PAC1 is expressed in several central nervous system (CNS) regions, including the hippocampal formation. Here we examined the effect of PAC1 receptor activation on alpha-secretase cleavage of the amyloid precursor protein (APP) and the production of secreted APP (APPsalpha).
Key findings
- Its specific G protein-coupled receptor PAC1 is expressed in several central nervous system (CNS) regions, including the hippocampal formation.
- Here we examined the effect of PAC1 receptor activation on alpha-secretase cleavage of the amyloid precursor protein (APP) and the production of secreted APP (APPsalpha).
- Stimulation of endogenously expressed PAC1 receptors with PACAP in human neuroblastoma cells increased APPsalpha secretion, which was completely inhibited by the PAC1 receptor specific antagonist PACAP-(6-38).
- In HEK cells stably overexpressing functional PAC1 receptors, PACAP-27 and PACAP-38 strongly stimulated alpha-secretase cleavage of APP.
Why it matters
In human neuroblastoma cells, activating the PAC1 receptor with PACAP increased the non-amyloidogenic processing of APP. This was a cell study, so it does not show that PACAP can treat or prevent Alzheimer's disease in people.
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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, 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 (FASEB journal : official publication of the Federation of American Societies for Experimental Biology) |
| Journal's citation record | 3 / 4 | The FASEB Journal: journal h-index 401 (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 118 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.4 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 3 / 6 | Cited 4.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Falk Fahrenholz: h-index 52 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Johannes Gutenberg University Mainz: institution h-index 934 (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 16401644) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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. Check the citation against the original before you use it.
APA 7th
Kojro, E., Postina, R., Buro, C., Meiringer, C., Gehrig-Burger, K., & Fahrenholz, F. (2006). The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.05-4812fje
Vancouver
Kojro E, Postina R, Buro C, Meiringer C, Gehrig-Burger K, Fahrenholz F. The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006. doi:10.1096/fj.05-4812fje. PMID: 16401644.
BibTeX
@article{kojro2006-16401644,
author = {Kojro, E. and Postina, R. and Buro, C. and Meiringer, C. and Gehrig-Burger, K. and Fahrenholz, F.},
title = {{The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein}},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2006},
doi = {10.1096/fj.05-4812fje},
pmid = {16401644},
url = {https://doi.org/10.1096/fj.05-4812fje}
}
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