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Frontotemporal Dementia Patient Neurons With Progranulin Deficiency Display Protein Dyshomeostasis
Lisa Elia, Bianca Herting, Amela Alijagic, Christina Buselli, Leela Wong, Grace Morrison, Miguel A Prado, Joao A Paulo et al.. bioRxiv : the preprint server for biology, 2023-01-20
Topic: Disease mechanisms in lab and animal studies
Haploinsufficiency of progranulin (PGRN) causes frontotemporal dementia (FTD), a devastating neurodegenerative disease with no effective treatment. PGRN is required for efficient proteostasis, as loss of neuronal PGRN results in dysfunctional lysosomes and impaired clearance and cytoplasmic aggregation of TDP-43, a protein involved in neurodegeneration in FTD. These and other events lead to neurodegeneration and neuroinflammation. However, the detailed mechanisms leading to protein dyshomeostasis in PGRN-deficient cells remain unclear. We report here the development of human cell models of FTD with PGRN-deficiency to explore the molecular mechanisms underlying proteostasis breakdown and TDP-43 aggregation in FTD. Neurons differentiated from FTD patient induced pluripotent stem cells (iPSCs) have reduced PGRN levels, and the neurons recapitulate key disease features, including impaired lysosomal function, defective TDP-43 turnover and accumulation, neurodegeneration, and death. Proteomic analysis revealed altered levels of proteins linked to the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS) in FTD patient neurons, providing new mechanistic insights into the link between PGRN-deficiency and disease pathobiology.
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APA 7th
Elia, L., Herting, B., Alijagic, A., Buselli, C., Wong, L., Morrison, G., et al. (2023). Frontotemporal Dementia Patient Neurons With Progranulin Deficiency Display Protein Dyshomeostasis. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2023.01.18.524611
Vancouver
Elia L, Herting B, Alijagic A, Buselli C, Wong L, Morrison G, et al. Frontotemporal Dementia Patient Neurons With Progranulin Deficiency Display Protein Dyshomeostasis. bioRxiv : the preprint server for biology. 2023. doi:10.1101/2023.01.18.524611. PMID: 36712069.
BibTeX
@article{elia2023-36712069,
author = {Elia, Lisa and Herting, Bianca and Alijagic, Amela and Buselli, Christina and Wong, Leela and Morrison, Grace and Prado, Miguel A and Paulo, Joao A and others},
title = {{Frontotemporal Dementia Patient Neurons With Progranulin Deficiency Display Protein Dyshomeostasis}},
journal = {bioRxiv : the preprint server for biology},
year = {2023},
doi = {10.1101/2023.01.18.524611},
pmid = {36712069},
url = {https://doi.org/10.1101/2023.01.18.524611}
}
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Key findings
- PGRN is required for efficient proteostasis, as loss of neuronal PGRN results in dysfunctional lysosomes and impaired clearance and cytoplasmic aggregation of TDP-43, a protein involved in neurodegeneration in FTD.
- Proteomic analysis revealed altered levels of proteins linked to the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS) in FTD patient neurons, providing new mechanistic insights into the link between PGRN-deficiency and disease pathobiology.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 20 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 12 of the 60 points we could judge it on, which is 20 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv : the preprint server for biology) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 3 / 5 | 2023 — 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) |
| 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 36712069) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 12 / 60 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 12 of the 60 points we could judge it on is 20 out of 100. |
| Total | 20 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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