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The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein
Delarasse C, Auger R, Gonnord P, Fontaine B, Kanellopoulos JM.. The Journal of biological chemistry, 2010-11-16
Topic: Brain proteins, microglia and lab models
The amyloid precursor protein (APP) is cleaved by β- and γ-secretases to generate the β-amyloid (Aβ) peptides, which are present in large amounts in the amyloid plaques of Alzheimer disease (AD) patient brains. Non-amyloidogenic processing of APP by α-secretases leads to proteolytic cleavage within the Aβ peptide sequence and shedding of the soluble APP ectodomain (sAPPα), which has been reported to be endowed with neuroprotective properties. In this work, we have shown that activation of the purinergic receptor P2X7 (P2X7R) stimulates sAPPα release from mouse neuroblastoma cells expressing human APP, from human neuroblastoma cells and from mouse primary astrocytes or neural progenitor cells. sAPPα shedding is inhibited by P2X7R antagonists or knockdown of P2X7R with specific small interfering RNA (siRNA) and is not observed in neural cells from P2X7R-deficient mice.
Key findings
- Non-amyloidogenic processing of APP by α-secretases leads to proteolytic cleavage within the Aβ peptide sequence and shedding of the soluble APP ectodomain (sAPPα), which has been reported to be endowed with neuroprotective properties.
- In this work, we have shown that activation of the purinergic receptor P2X7 (P2X7R) stimulates sAPPα release from mouse neuroblastoma cells expressing human APP, from human neuroblastoma cells and from mouse primary astrocytes or neural progenitor cells. sAPPα shedding is inhibited by P2X7R antagonists or knockdown of P2X7R with specific small interfering RNA (siRNA) and is not observed in neural cells from P2X7R-deficient mice.
- P2X7R-dependent APP-cleavage is independent of extracellular calcium and strongly inhibited by hydroxamate-based metalloprotease inhibitors, TAPI-2 and GM6001.
- However, knockdown of a disintegrin and metalloproteinase-9 (ADAM9), ADAM10 and ADAM17 by specific siRNA, known to have α-secretase activity, does not block the P2X7R-dependent non-amyloidogenic pathway.
Why it matters
In mouse and human neural cells, activating the P2X7 receptor increased release of the neuroprotective sAPPα fragment. These are cell and animal findings, so it is not yet known whether this could be used to treat or prevent Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 44/100
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 | 2011 — 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 | 5 / 7 | Cited 109 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.4 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 4.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jean Kanellopoulos: h-index 42 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,511 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21081501) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
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Read the original
- DOI: 10.1074/jbc.m110.200618
- PubMed: 21081501
- 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
Delarasse, C., Auger, R., Gonnord, P., Fontaine, B., & Kanellopoulos, J. M. (2011). The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m110.200618
Vancouver
Delarasse C, Auger R, Gonnord P, Fontaine B, Kanellopoulos JM. The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein. The Journal of biological chemistry. 2011. doi:10.1074/jbc.m110.200618. PMID: 21081501.
BibTeX
@article{delarasse2011-21081501,
author = {Delarasse, C. and Auger, R. and Gonnord, P. and Fontaine, B. and Kanellopoulos, J. M.},
title = {{The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein}},
journal = {The Journal of biological chemistry},
year = {2011},
doi = {10.1074/jbc.m110.200618},
pmid = {21081501},
url = {https://doi.org/10.1074/jbc.m110.200618}
}
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