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Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology
Tramutola A, Di Domenico F, Barone E, Arena A, Giorgi A, di Francesco L, Schininà ME, Coccia R et al.. Antioxidants & redox signaling, 2016-10-26
Topic: Brain proteins, microglia and lab models
Aims Among the putative mechanisms proposed to be common factors in Down syndrome (DS) and Alzheimer's disease (AD) neuropathology, deficits in protein quality control (PQC) have emerged as a unifying mechanism of neurodegeneration. Considering that disturbance of protein degradation systems is present in DS and that oxidized/misfolded proteins require polyubiquitinylation for degradation via the ubiquitin proteasome system, this study investigated if dysregulation of protein polyubiquitinylation is associated with AD neurodegeneration in DS. Results Postmortem brains from DS cases before and after development of AD neuropathology and age-matched controls were analyzed. By selectively isolating polyubiquitinated proteins, we were able to identify specific proteins with an altered pattern of polyubiquitinylation as a function of age. Interestingly, we found that oxidation is coupled with polyubiquitinylation for most proteins mainly involved in PQC and energy metabolism. Innovation This is the first study showing alteration of the polyubiquitinylation profile as a function of aging in DS brain compared with healthy controls. Understanding the onset of the altered ubiquitome profile in DS brain may contribute to identification of key molecular regulators of age-associated cognitive decline. Conclusions Disturbance of the polyubiquitinylation machinery may be a key feature of aging and neurodegeneration. In DS, age-associated deficits of the proteolytic system may further exacerbate the accumulation of oxidized/misfolded/polyubiquitinated proteins, which is not efficiently degraded and may become harmful to neurons and contribute to AD neuropathology. Antioxid. Redox Signal. 26, 280-298.
Key findings
- Considering that disturbance of protein degradation systems is present in DS and that oxidized/misfolded proteins require polyubiquitinylation for degradation via the ubiquitin proteasome system, this study investigated if dysregulation of protein polyubiquitinylation is associated with AD neurodegeneration in DS.
- Results Postmortem brains from DS cases before and after development of AD neuropathology and age-matched controls were analyzed.
- Interestingly, we found that oxidation is coupled with polyubiquitinylation for most proteins mainly involved in PQC and energy metabolism.
- Innovation This is the first study showing alteration of the polyubiquitinylation profile as a function of aging in DS brain compared with healthy controls.
Why it matters
In postmortem Down syndrome brains, the pattern of protein tagging for degradation changed with age and Alzheimer pathology. This is a small tissue study and does not test treatment, cure, or prevention.
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 (Antioxidants & redox signaling) |
| Journal's citation record | 3 / 4 | Antioxidants and Redox Signaling: journal h-index 274 (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 | 2 / 5 | 2017 — within 10 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 | 4 / 7 | Cited 49 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 3 / 6 | Cited 3.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 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) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27627691) |
| 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 →
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APA 7th
Tramutola, A., Di Domenico, F., Barone, E., Arena, A., Giorgi, A., di Francesco, L., et al. (2017). Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology. Antioxidants & redox signaling. https://doi.org/10.1089/ars.2016.6686
Vancouver
Tramutola A, Di Domenico F, Barone E, Arena A, Giorgi A, di Francesco L, et al. Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology. Antioxidants & redox signaling. 2017. doi:10.1089/ars.2016.6686. PMID: 27627691.
BibTeX
@article{tramutola2017-27627691,
author = {Tramutola, A. and Di Domenico, F. and Barone, E. and Arena, A. and Giorgi, A. and di Francesco, L. and Schininà, M. E. and Coccia, R. and others},
title = {{Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology}},
journal = {Antioxidants \& redox signaling},
year = {2017},
doi = {10.1089/ars.2016.6686},
pmid = {27627691},
url = {https://doi.org/10.1089/ars.2016.6686}
}
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