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Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome
Mathieu Bourdenx, Adrián Martín-Segura, Aurora Scrivo, Jose A Rodriguez-Navarro, Susmita Kaushik, Inmaculada Tasset, Antonio Diaz, Nadia J Storm et al.. Cell, 2021-04-22
Topic: Disease mechanisms in lab and animal studies
Components of the proteostasis network malfunction in aging, and reduced protein quality control in neurons has been proposed to promote neurodegeneration. Here, we investigate the role of chaperone-mediated autophagy (CMA), a selective autophagy shown to degrade neurodegeneration-related proteins, in neuronal proteostasis. Using mouse models with systemic and neuronal-specific CMA blockage, we demonstrate that loss of neuronal CMA leads to altered neuronal function, selective changes in the neuronal metastable proteome, and proteotoxicity, all reminiscent of brain aging. Imposing CMA loss on a mouse model of Alzheimer's disease (AD) has synergistic negative effects on the proteome at risk of aggregation, thus increasing neuronal disease vulnerability and accelerating disease progression. Conversely, chemical enhancement of CMA ameliorates pathology in two different AD experimental mouse models. We conclude that functional CMA is essential for neuronal proteostasis through the maintenance of a subset of the proteome with a higher risk of misfolding than the general proteome.
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APA 7th
Bourdenx, M., Martín-Segura, A., Scrivo, A., Rodriguez-Navarro, J. A., Kaushik, S., Tasset, I., et al. (2021). Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell. https://doi.org/10.1016/j.cell.2021.03.048
Vancouver
Bourdenx M, Martín-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S, Tasset I, et al. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell. 2021. doi:10.1016/j.cell.2021.03.048. PMID: 33891876.
BibTeX
@article{bourdenx2021-33891876,
author = {Bourdenx, Mathieu and Martín-Segura, Adrián and Scrivo, Aurora and Rodriguez-Navarro, Jose A and Kaushik, Susmita and Tasset, Inmaculada and Diaz, Antonio and Storm, Nadia J and others},
title = {{Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome}},
journal = {Cell},
year = {2021},
doi = {10.1016/j.cell.2021.03.048},
pmid = {33891876},
url = {https://doi.org/10.1016/j.cell.2021.03.048}
}
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Key findings
- We conclude that functional CMA is essential for neuronal proteostasis through the maintenance of a subset of the proteome with a higher risk of misfolding than the general proteome.
Study details
- Evidence strengthLow
How this study scored 41/100
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, 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, multicenter collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| 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 | 3 / 5 | 2021 — within 6 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 | — / 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33891876) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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