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Autophagy modulates Aβ accumulation and formation of aggregates in yeast
Prashant R Bharadwaj, Ralph N Martins. Molecular and cellular neurosciences, 2020-01-18
Topic: Disease mechanisms in lab and animal studies
Intracellular accumulation of amyloid-β protein (Aβ) is an early event in Alzheimer's disease (AD). The autophagy-lysosomal pathway is an important pathway for maintaining cellular proteostasis and for the removal of damaged organelles and protein aggregates in all eukaryotes. Despite mounting evidence showing that modulating autophagy promotes clearance of Aβ aggregates, the regulatory mechanisms and signalling pathways underlying this process remain poorly understood. In order to gain better insight we used our previously characterised yeast model expressing GFP-Aβ42 to identify genes that regulate the removal of Aβ42 aggregates by autophagy. We report that GFP-Aβ42 is sequestered and is selectively transported to vacuole for degradation and that autophagy is the prominent pathway for clearance of aggregates. Next, to identify genes that selectively promote the removal of Aβ42 aggregates, we screened levels of GFP-Aβ42 and non-aggregating GFP-Aβ42 (19:34) proteins in a panel of 192 autophagy mutants lacking genes involved in regulation and initiation of the pathway, cargo selection and degradation processes. The nutrient and stress signalling genes RRD1, SNF4, GCN4 and SSE1 were identified. Deletion of these genes impaired GFP-Aβ42 clearance and their overexpression reduced GFP-Aβ42 levels in yeast. Overall, our findings identify a novel role for these nutrient and stress signalling genes in the targeted elimination of Aβ42 aggregates, which offer a promising avenue for developing autophagy based therapies to suppress amyloid deposition in AD.
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APA 7th
Bharadwaj, P. R., & Martins, R. N. (2020). Autophagy modulates Aβ accumulation and formation of aggregates in yeast. Molecular and cellular neurosciences. https://doi.org/10.1016/j.mcn.2020.103466
Vancouver
Bharadwaj PR, Martins RN. Autophagy modulates Aβ accumulation and formation of aggregates in yeast. Molecular and cellular neurosciences. 2020. doi:10.1016/j.mcn.2020.103466. PMID: 31962153.
BibTeX
@article{bharadwaj2020-31962153,
author = {Bharadwaj, Prashant R and Martins, Ralph N},
title = {{Autophagy modulates Aβ accumulation and formation of aggregates in yeast}},
journal = {Molecular and cellular neurosciences},
year = {2020},
doi = {10.1016/j.mcn.2020.103466},
pmid = {31962153},
url = {https://doi.org/10.1016/j.mcn.2020.103466}
}
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Key findings
- Overall, our findings identify a novel role for these nutrient and stress signalling genes in the targeted elimination of Aβ42 aggregates, which offer a promising avenue for developing autophagy based therapies to suppress amyloid deposition in AD.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported 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 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and cellular neurosciences) |
| 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 | 2 / 5 | 2020 — 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 | Laboratory or animal study (title names “yeast”) — scores zero |
| 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 31962153) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
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