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ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons
Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S et al.. The EMBO journal, 2010-07-30
Topic: Brain proteins, microglia and lab models
The amyloid precursor protein (APP) undergoes constitutive shedding by a protease activity called alpha-secretase. This is considered an important mechanism preventing the generation of the Alzheimer's disease amyloid-beta peptide (Abeta). alpha-Secretase appears to be a metalloprotease of the ADAM family, but its identity remains to be established. Using a novel alpha-secretase-cleavage site-specific antibody, we found that RNAi-mediated knockdown of ADAM10, but surprisingly not of ADAM9 or 17, completely suppressed APP alpha-secretase cleavage in different cell lines and in primary murine neurons. Other proteases were not able to compensate for this loss of alpha-cleavage. This finding was further confirmed by mass-spectrometric detection of APP-cleavage fragments. Surprisingly, in different cell lines, the reduction of alpha-secretase cleavage was not paralleled by a corresponding increase in the Abeta-generating beta-secretase cleavage, revealing that both proteases do not always compete for APP as a substrate. Instead, our data suggest a novel pathway for APP processing, in which ADAM10 can partially compete with gamma-secretase for the cleavage of a C-terminal APP fragment generated by beta-secretase. We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.
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APA 7th
Kuhn, P. H., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., et al. (2010). ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. The EMBO journal. https://doi.org/10.1038/emboj.2010.167
Vancouver
Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, et al. ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. The EMBO journal. 2010. doi:10.1038/emboj.2010.167. PMID: 20676056.
BibTeX
@article{kuhn2010-20676056,
author = {Kuhn, P. H. and Wang, H. and Dislich, B. and Colombo, A. and Zeitschel, U. and Ellwart, J. W. and Kremmer, E. and Rossner, S. and others},
title = {{ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons}},
journal = {The EMBO journal},
year = {2010},
doi = {10.1038/emboj.2010.167},
pmid = {20676056},
url = {https://doi.org/10.1038/emboj.2010.167}
}
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Key findings
- Using a novel alpha-secretase-cleavage site-specific antibody, we found that RNAi-mediated knockdown of ADAM10, but surprisingly not of ADAM9 or 17, completely suppressed APP alpha-secretase cleavage in different cell lines and in primary murine neurons.
- We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.
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Study details
- Evidence strengthLow
How this study scored 36/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The EMBO journal) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2010 — 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20676056) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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