Home › Research › Disease mechanisms
Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins
David Salcedo-Tacuma, Nadeem Asad, Md Qamrul Islam, Raymond Anderson, David M Smith. Science advances, 2025-10-10
Topic: Disease mechanisms in lab and animal studies
Age-related proteinopathies, including Alzheimer's and Parkinson's disease, are driven by toxic accumulation of misfolded and intrinsically disordered proteins (IDPs) that overwhelm cellular proteostasis. The proteasome clears these proteins, but its failure in disease remains unclear. We engineered a Caenorhabditis elegans model with a hyperactive 20S proteasome (α3ΔN) for selective 20S activation. α3ΔN markedly enhanced IDP and misfolded protein degradation, reduced oxidative damage, and improved endoplasmic reticulum-associated degradation (ERAD). Aggregation-prone substrates such as vitellogenins and human alpha-1 antitrypsin (ATZ) were efficiently cleared. Integrated proteomic and transcriptomic analyses reveal systemic adaptations featuring increased protein turnover and oxidative stress resistance independent of superoxide dismutases (SODs). Notably, α3ΔN extended life span and stress resistance independently of canonical unfolded protein response (UPR) signaling via xbp-1. These findings substantiate a "20S pathway" of proteostasis that directly alleviates protein aggregation and oxidative stress, offering a promising therapeutic angle for neurodegenerative diseases.
Key findings
- These findings substantiate a "20S pathway" of proteostasis that directly alleviates protein aggregation and oxidative stress, offering a promising therapeutic angle for neurodegenerative diseases.
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 and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science advances) |
| 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 | 4 / 5 | 2025 — within 3 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 | Laboratory or animal study (title names “c. elegans”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41071871) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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. Check the citation against the original before you use it.
APA 7th
Salcedo-Tacuma, D., Asad, N., Islam, M. Q., Anderson, R., & Smith, D. M. (2025). Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins. Science advances. https://doi.org/10.1126/sciadv.adx3014
Vancouver
Salcedo-Tacuma D, Asad N, Islam MQ, Anderson R, Smith DM. Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins. Science advances. 2025. doi:10.1126/sciadv.adx3014. PMID: 41071871.
BibTeX
@article{salcedotacuma2025-41071871,
author = {Salcedo-Tacuma, David and Asad, Nadeem and Islam, Md Qamrul and Anderson, Raymond and Smith, David M},
title = {{Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins}},
journal = {Science advances},
year = {2025},
doi = {10.1126/sciadv.adx3014},
pmid = {41071871},
url = {https://doi.org/10.1126/sciadv.adx3014}
}
Related studies in Disease mechanisms
Also tagged “autophagy”
240 studies in the library carry the topic tag “autophagy”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 240 tagged studies.