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Upregulation of SET expression by BACE1 and its implications in Down syndrome
Zhang X, Wu Y, Duan X, Chen W, Zou H, Zhang M, Zhang S, Cai F et al.. Molecular neurobiology, 2014-06-17
Topic: Brain proteins, microglia and lab models
Down syndrome (DS) is one of the most common genetic diseases. Patients with DS display growth delay and intellectual disabilities and develop Alzheimer's disease (AD) neuropathology after middle age, including neuritic plaques and neurofibrillary tangles. Beta-site amyloid β precursor protein (APP) cleaving enzyme 1 (BACE1), essential for Aβ production and neuritic plaque formation, is elevated in DS patients. However, its homolog, β-site APP cleaving enzyme 2 (BACE2), functions as θ-secretase and plays a differential role in plaque formation. In this study, by using Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE) and LC-MS/MS proteomic profiling analysis, we found that the SET oncogene protein (SET) expression was associated with BACE1 but not BACE2. SET protein was increased in BACE1 overexpressing cells and was markedly reduced in the BACE1 knockout mice. We found that the overexpression of BACE1 or SET significantly inhibited cell proliferation. Moreover, knockdown of SET in BACE1 overexpression cells significantly rescued BACE1-induced cell growth suppression. Furthermore, both BACE1 and SET protein levels were increased in Down syndrome patients. It suggests that BACE1 overexpression-induced SET upregulation may contribute to growth delay and cognitive impairment in DS patients. Our work provides a new insight that BACE1 overexpression not only promotes neuritic plaque formation but may also potentiate neurodegeneration mediated by SET elevation in Alzheimer-associated dementia in DS.
Key findings
- In this study, by using Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE) and LC-MS/MS proteomic profiling analysis, we found that the SET oncogene protein (SET) expression was associated with BACE1 but not BACE2.
- We found that the overexpression of BACE1 or SET significantly inhibited cell proliferation.
- Moreover, knockdown of SET in BACE1 overexpression cells significantly rescued BACE1-induced cell growth suppression.
- It suggests that BACE1 overexpression-induced SET upregulation may contribute to growth delay and cognitive impairment in DS patients.
Why it matters
In cell and mouse experiments, BACE1 but not BACE2 was associated with increased SET protein, and both BACE1 and SET levels were increased in Down syndrome patients. The authors suggest BACE1-induced SET upregulation may contribute to growth delay and cognitive impairment in Down syndrome, but this is laboratory work and no treatment was tested in people.
Study details
- Evidence strengthLow
How this study scored 32/100
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 (Molecular neurobiology) |
| Journal's citation record | 2 / 4 | Molecular Neurobiology: journal h-index 176 (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 | 2015 — 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 | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 1 / 6 | Cited 1.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Weihong Song: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of British Columbia: institution h-index 1,424 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24935721) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 32 / 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. 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
Zhang, X., Wu, Y., Duan, X., Chen, W., Zou, H., Zhang, M., et al. (2015). Upregulation of SET expression by BACE1 and its implications in Down syndrome. Molecular neurobiology. https://doi.org/10.1007/s12035-014-8782-x
Vancouver
Zhang X, Wu Y, Duan X, Chen W, Zou H, Zhang M, et al. Upregulation of SET expression by BACE1 and its implications in Down syndrome. Molecular neurobiology. 2015. doi:10.1007/s12035-014-8782-x. PMID: 24935721.
BibTeX
@article{zhang2015-24935721,
author = {Zhang, X. and Wu, Y. and Duan, X. and Chen, W. and Zou, H. and Zhang, M. and Zhang, S. and Cai, F. and others},
title = {{Upregulation of SET expression by BACE1 and its implications in Down syndrome}},
journal = {Molecular neurobiology},
year = {2015},
doi = {10.1007/s12035-014-8782-x},
pmid = {24935721},
url = {https://doi.org/10.1007/s12035-014-8782-x}
}
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