Quantitative interaction proteomics of neurodegenerative disease proteins
Hosp F, Vossfeldt H, Heinig M, Vasiljevic D, Arumughan A, Wyler E, Genetic and Environmental Risk for Alzheimer’s Disease GERAD1 Consortium, Landthaler M et al.. Cell reports, 2015-05-07
Topic: Brain proteins, microglia and lab models
Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.
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APA 7th
Hosp, F., Vossfeldt, H., Heinig, M., Vasiljevic, D., Arumughan, A., Wyler, E., et al. (2015). Quantitative interaction proteomics of neurodegenerative disease proteins. Cell reports. https://doi.org/10.1016/j.celrep.2015.04.030
Vancouver
Hosp F, Vossfeldt H, Heinig M, Vasiljevic D, Arumughan A, Wyler E, et al. Quantitative interaction proteomics of neurodegenerative disease proteins. Cell reports. 2015. doi:10.1016/j.celrep.2015.04.030. PMID: 25959826.
BibTeX
@article{hosp2015-25959826,
author = {Hosp, F. and Vossfeldt, H. and Heinig, M. and Vasiljevic, D. and Arumughan, A. and Wyler, E. and {Genetic and Environmental Risk for Alzheimer’s Disease GERAD1 Consortium} and Landthaler, M. and others},
title = {{Quantitative interaction proteomics of neurodegenerative disease proteins}},
journal = {Cell reports},
year = {2015},
doi = {10.1016/j.celrep.2015.04.030},
pmid = {25959826},
url = {https://doi.org/10.1016/j.celrep.2015.04.030}
}
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Key findings
- Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed 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 and multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports) |
| 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 | 1 / 5 | 2015 — within 20 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 25959826) |
| Free to read | 2 / 2 | Free to read |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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