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Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease
Di Domenico F, Pupo G, Tramutola A, Giorgi A, Schininà ME, Coccia R, Head E, Butterfield DA et al.. Free radical biology & medicine, 2014-03-25
Topic: Brain proteins, microglia and lab models
Down syndrome (DS) is the most common genetic cause of intellectual disability, due to partial or complete triplication of chromosome 21. DS subjects are characterized by a number of abnormalities including premature aging and development of Alzheimer disease (AD) neuropathology after approximately 40 years of age. Several studies show that oxidative stress plays a crucial role in the development of neurodegeneration in the DS population. Increased lipid peroxidation is one of the main events causing redox imbalance within cells through the formation of toxic aldehydes that easily react with DNA, lipids, and proteins. In this study we used a redox proteomics approach to identify specific targets of 4-hydroxynonenal modifications in the frontal cortex from DS cases with and without AD pathology. We suggest that a group of identified proteins followed a specific pattern of oxidation in DS vs young controls, probably indicating characteristic features of the DS phenotype; a second group of identified proteins showed increased oxidation in DS/AD vs DS, thus possibly playing a role in the development of AD. The third group of comparison, DS/AD vs old controls, identified proteins that may be considered specific markers of AD pathology. All the identified proteins are involved in important biological functions including intracellular quality control systems, cytoskeleton network, energy metabolism, and antioxidant response. Our results demonstrate that oxidative damage is an early event in DS, as well as dysfunctions of protein-degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to oxidative damage accumulation that might contribute to AD development. Further, considering that the majority of proteins have been already demonstrated to be oxidized in AD brain, our results strongly support similarities with AD in DS.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Di Domenico, F., Pupo, G., Tramutola, A., Giorgi, A., Schininà, M. E., Coccia, R., et al. (2014). Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease. Free radical biology & medicine. https://doi.org/10.1016/j.freeradbiomed.2014.03.027
Vancouver
Di Domenico F, Pupo G, Tramutola A, Giorgi A, Schininà ME, Coccia R, et al. Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease. Free radical biology & medicine. 2014. doi:10.1016/j.freeradbiomed.2014.03.027. PMID: 24675226.
BibTeX
@article{didomenico2014-24675226,
author = {Di Domenico, F. and Pupo, G. and Tramutola, A. and Giorgi, A. and Schininà, M. E. and Coccia, R. and Head, E. and Butterfield, D. A. and others},
title = {{Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease}},
journal = {Free radical biology \& medicine},
year = {2014},
doi = {10.1016/j.freeradbiomed.2014.03.027},
pmid = {24675226},
url = {https://doi.org/10.1016/j.freeradbiomed.2014.03.027}
}
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.
Key findings
- We suggest that a group of identified proteins followed a specific pattern of oxidation in DS vs young controls, probably indicating characteristic features of the DS phenotype; a second group of identified proteins showed increased oxidation in DS/AD vs DS, thus possibly playing a role in the development of AD.
- Our results demonstrate that oxidative damage is an early event in DS, as well as dysfunctions of protein-degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to oxidative damage accumulation that might contribute to AD development.
- Further, considering that the majority of proteins have been already demonstrated to be oxidized in AD brain, our results strongly support similarities with AD in DS.
Why it matters
People with Down syndrome develop Alzheimer's-type brain changes after about age 40, and this study searched post-mortem frontal cortex from Down syndrome brains with and without that pathology, plus young and old controls, for proteins damaged by 4-hydroxynonenal, a toxic product of fat oxidation. The damaged proteins work in protein quality control, cell structure, energy use and antioxidant defence, and the authors note that most have already been reported as oxidised in Alzheimer's brain. They read this as a sign that oxidative damage starts early in Down syndrome and "might contribute" to Alzheimer's, but a post-mortem comparison cannot show cause, and the study tests no treatment.
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 randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Free radical biology & medicine) |
| Journal's citation record | 3 / 4 | Free Radical Biology and Medicine: journal h-index 378 (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 | 2014 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 99 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.1 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 26 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Marzia Perluigi: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sapienza University of Rome: institution h-index 1,145 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24675226) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.freeradbiomed.2014.03.027
- PubMed: 24675226
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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