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A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism
Vanessa Lage-Rupprecht, Bruce Schultz, Justus Dick, Marcin Namysl, Andrea Zaliani, Stephan Gebel, Ole Pless, Jeanette Reinshagen et al.. Patterns (New York, N.Y.), 2022-01-26
Topic: Disease mechanisms in lab and animal studies
Plain-language summary
The high number of failed pre-clinical and clinical studies for compounds targeting Alzheimer disease (AD) has demonstrated that there is a need to reassess existing strategies. Here, we pursue a holistic, mechanism-centric drug repurposing approach combining computational analytics and experimental screening data. Based on this integrative workflow, we identified 77 druggable modifiers of tau phosphorylation (pTau). One of the upstream modulators of pTau, HDAC6, was screened with 5,632 drugs in a tau-specific assay, resulting in the identification of 20 repurposing candidates. Four compounds and their known targets were found to have a link to AD-specific genes. Our approach can be applied to a variety of AD-associated pathophysiological mechanisms to identify more repurposing candidates.
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APA 7th
Lage-Rupprecht, V., Schultz, B., Dick, J., Namysl, M., Zaliani, A., Gebel, S., et al. (2022). A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism. Patterns (New York, N.Y.). https://doi.org/10.1016/j.patter.2021.100433
Vancouver
Lage-Rupprecht V, Schultz B, Dick J, Namysl M, Zaliani A, Gebel S, et al. A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism. Patterns (New York, N.Y.). 2022. doi:10.1016/j.patter.2021.100433. PMID: 35510183.
BibTeX
@article{lagerupprecht2022-35510183,
author = {Lage-Rupprecht, Vanessa and Schultz, Bruce and Dick, Justus and Namysl, Marcin and Zaliani, Andrea and Gebel, Stephan and Pless, Ole and Reinshagen, Jeanette and others},
title = {{A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism}},
journal = {Patterns (New York, N.Y.)},
year = {2022},
doi = {10.1016/j.patter.2021.100433},
pmid = {35510183},
url = {https://doi.org/10.1016/j.patter.2021.100433}
}
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Key findings
- The high number of failed pre-clinical and clinical studies for compounds targeting Alzheimer disease (AD) has demonstrated that there is a need to reassess existing strategies.
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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 (Patterns (New York, N.Y.)) |
| 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 | 2022 — 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 35510183) |
| 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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