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Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease
Belyaev ND, Nalivaeva NN, Makova NZ, Turner AJ.. EMBO reports, 2008-12-05
Topic: Brain proteins, microglia and lab models
Amyloid beta-peptide (Abeta) accumulation leads to neurodegeneration and Alzheimer disease; however, amyloid metabolism is a dynamic process and enzymic mechanisms exist for Abeta removal. Considerable controversy surrounds whether the intracellular domain of the amyloid precursor protein (AICD) regulates expression of the Abeta-degrading metalloprotease, neprilysin (NEP). By comparing two neuroblastoma cell lines differing substantially in NEP expression, we show by chromatin immunoprecipitation (ChIP) that AICD is bound directly to the NEP promoter in high NEP-expresser (NB7) cells but not in low-expresser (SH-SY5Y) cells.
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APA 7th
Belyaev, N. D., Nalivaeva, N. N., Makova, N. Z., & Turner, A. J. (2009). Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease. EMBO reports. https://doi.org/10.1038/embor.2008.222
Vancouver
Belyaev ND, Nalivaeva NN, Makova NZ, Turner AJ. Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease. EMBO reports. 2009. doi:10.1038/embor.2008.222. PMID: 19057576.
BibTeX
@article{belyaev2009-19057576,
author = {Belyaev, N. D. and Nalivaeva, N. N. and Makova, N. Z. and Turner, A. J.},
title = {{Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease}},
journal = {EMBO reports},
year = {2009},
doi = {10.1038/embor.2008.222},
pmid = {19057576},
url = {https://doi.org/10.1038/embor.2008.222}
}
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Key findings
- Considerable controversy surrounds whether the intracellular domain of the amyloid precursor protein (AICD) regulates expression of the Abeta-degrading metalloprotease, neprilysin (NEP).
- By comparing two neuroblastoma cell lines differing substantially in NEP expression, we show by chromatin immunoprecipitation (ChIP) that AICD is bound directly to the NEP promoter in high NEP-expresser (NB7) cells but not in low-expresser (SH-SY5Y) cells.
- The methylation status of the NEP promoter does not regulate expression in these cells, whereas the histone deacetylase inhibitors trichostatin A and valproate partly restore NEP expression and activity in SH-SY5Y cells.
- ChIP analysis also reveals AICD binding to the NEP promoter in rat primary neurons but not in HUVEC cells.
Why it matters
In two neuroblastoma cell lines, the amyloid precursor protein intracellular domain bound directly to the neprilysin promoter in high-expressing cells but not in low-expressing cells. This is a cell-based finding about amyloid removal and does not show that altering neprilysin treats or prevents Alzheimer's disease.
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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 (EMBO reports) |
| Journal's citation record | 3 / 4 | EMBO Reports: journal h-index 252 (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 | 5 / 7 | Cited 177 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.3 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 8.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 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 | 3 / 4 | Last-listed author Anthony J. Turner: h-index 80 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Leeds: institution h-index 950 (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 19057576) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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