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Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain
Shim KS, Bergelson JM, Furuse M, Ovod V, Krude T, Lubec G.. Journal of neural transmission. Supplementum, 2003-01-01
Topic: Brain proteins, microglia and lab models
Trisomy 21 (Down syndrome, DS) is the most common genetic cause of mental retardation, resulting from triplication of the whole or distal part of human chromosome 21. Overexpression of genes located on chromosome 21, as a result of extra gene load, has been considered a central hypothesis for the explanation of the DS phenotype. This gene dosage hypothesis has been challenged, however. We have therefore decided to study proteins whose genes are encoded on chromosome 21 in brain of patients with DS and Alzheimer's disease (AD), as all patients with DS from the fourth decade show Alzheimer-related neuropathology. Using immunoblotting we determined Coxsackievirus and adenovirus receptor (CAR), Claudin-8, C21orf2, Chromatin assembly factor 1 p60 subunit (CAF-1 p60) in frontal cortex from DS, AD and control patients. Significant reduction of C21orf2 and CAF-1 p60, but comparable expression of CAR and claudin-8 was observed in DS but all proteins were comparable to controls in AD, even when related to NSE levels to rule out neuronal cell loss or actin to normalise versus a housekeeping protein. Reduced CAF-1 p60 may reflect impaired DNA repair most probably due to oxidative stress found as early as in fetal life continuing into adulthood. The decrease of C21orf2 may represent mitochondrial dysfunction that has been reported repeatedly and also data on CAR and claudin-8 are not supporting the gene-dosage hypothesis at the protein level. As aberrant expression of the four proteins was not found in brains of patients with AD, decreased CAF and C21orf2 can be considered specific for DS.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Shim, K. S., Bergelson, J. M., Furuse, M., Ovod, V., Krude, T., & Lubec, G. (2003). Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain. Journal of neural transmission. Supplementum. https://doi.org/10.1007/978-3-7091-6721-2_10
Vancouver
Shim KS, Bergelson JM, Furuse M, Ovod V, Krude T, Lubec G. Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain. Journal of neural transmission. Supplementum. 2003. doi:10.1007/978-3-7091-6721-2_10. PMID: 15068244.
BibTeX
@article{shim2003-15068244,
author = {Shim, K. S. and Bergelson, J. M. and Furuse, M. and Ovod, V. and Krude, T. and Lubec, G.},
title = {{Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain}},
journal = {Journal of neural transmission. Supplementum},
year = {2003},
doi = {10.1007/978-3-7091-6721-2_10},
pmid = {15068244},
url = {https://doi.org/10.1007/978-3-7091-6721-2_10}
}
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.
Key findings
- Overexpression of genes located on chromosome 21, as a result of extra gene load, has been considered a central hypothesis for the explanation of the DS phenotype.
- Significant reduction of C21orf2 and CAF-1 p60, but comparable expression of CAR and claudin-8 was observed in DS but all proteins were comparable to controls in AD, even when related to NSE levels to rule out neuronal cell loss or actin to normalise versus a housekeeping protein.
Why it matters
This study found reduced levels of C21orf2 and CAF-1 p60 proteins in the brain of people with Down syndrome, but these proteins were comparable to controls in Alzheimer's disease. The findings challenge the simple gene dosage hypothesis and do not provide a treatment or prevention.
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 randomized / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 35 of the 96 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neural transmission. Supplementum) |
| 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 | 2003 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 20 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.8 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 3 / 6 | Cited 4.2× 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 | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gert Lübec: h-index 70 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15068244) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 35 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 35 of the 96 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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