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Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons
Yi-Chen Hsieh, Zachary M Augur, Mason Arbery, Nancy Ashour, Katharine Barrett, Richard V Pearse, Earvin S Tio, Duc M Duong et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-03-12
Topic: Disease mechanisms in lab and animal studies
Neurons with lower basal UPS activity were more vulnerable to tau accumulation following mild UPS inhibition. Chronic reduction in proteasome activity in human neurons induced compensatory elevation of regulatory proteins involved in proteostasis and several proteasome subunits. These findings reveal that genetic variation influences basal UPS activity in human neurons and differentially sensitizes them to external factors perturbing the UPS, leading to the accumulation of aggregation-prone proteins such as tau. HIGHLIGHTS: Polygenic risk score for AD is associated with the ubiquitin-proteasome system (UPS) in neurons. Basal proteasome activity correlates with aggregation-prone protein levels in neurons. Genetic variation affects the response to proteasome inhibition in neurons. Neuronal proteasome perturbation induces an elevation in specific proteins involved in proteostasis. Low basal proteasome activity leads to enhanced tau accumulation with UPS challenge.
Key findings
- Neurons with lower basal UPS activity were more vulnerable to tau accumulation following mild UPS inhibition.
- Chronic reduction in proteasome activity in human neurons induced compensatory elevation of regulatory proteins involved in proteostasis and several proteasome subunits.
- These findings reveal that genetic variation influences basal UPS activity in human neurons and differentially sensitizes them to external factors perturbing the UPS, leading to the accumulation of aggregation-prone proteins such as tau.
- HIGHLIGHTS: Polygenic risk score for AD is associated with the ubiquitin-proteasome system (UPS) in neurons.
- Basal proteasome activity correlates with aggregation-prone protein levels in neurons.
Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people 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 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 2024 — 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 | 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 | — / 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 38470006) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Hsieh, Y.-C., Augur, Z. M., Arbery, M., Ashour, N., Barrett, K., Pearse, R. V., et al. (2024). Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.13680
Vancouver
Hsieh Y.-C, Augur ZM, Arbery M, Ashour N, Barrett K, Pearse RV, et al. Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.13680. PMID: 38470006.
BibTeX
@article{hsieh2024-38470006,
author = {Hsieh, Yi-Chen and Augur, Zachary M and Arbery, Mason and Ashour, Nancy and Barrett, Katharine and Pearse, Richard V and Tio, Earvin S and Duong, Duc M and others},
title = {{Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.13680},
pmid = {38470006},
url = {https://doi.org/10.1002/alz.13680}
}
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