A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism
© 2022 The Authors..
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.
| Errataetall: |
CommentIn: Patterns (N Y). 2022 Jun 10;3(6):100529. - PMID 35755871 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
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| Enthalten in: |
Patterns (New York, N.Y.) - 3(2022), 3 vom: 11. März, Seite 100433 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lage-Rupprecht, Vanessa [VerfasserIn] |
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| Links: |
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| Themen: |
Alzheimer disease |
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| Anmerkungen: |
Date Revised 16.07.2022 published: Electronic-eCollection CommentIn: Patterns (N Y). 2022 Jun 10;3(6):100529. - PMID 35755871 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.patter.2021.100433 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM340388331 |
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| 520 | |a © 2022 The Authors. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a computational modeling | |
| 650 | 4 | |a data integration | |
| 650 | 4 | |a drug repurposing | |
| 650 | 4 | |a in vitro screening | |
| 650 | 4 | |a knowledge graph | |
| 650 | 4 | |a tau phosphorylation | |
| 700 | 1 | |a Schultz, Bruce |e verfasserin |4 aut | |
| 700 | 1 | |a Dick, Justus |e verfasserin |4 aut | |
| 700 | 1 | |a Namysl, Marcin |e verfasserin |4 aut | |
| 700 | 1 | |a Zaliani, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Gebel, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Pless, Ole |e verfasserin |4 aut | |
| 700 | 1 | |a Reinshagen, Jeanette |e verfasserin |4 aut | |
| 700 | 1 | |a Ellinger, Bernhard |e verfasserin |4 aut | |
| 700 | 1 | |a Ebeling, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Esser, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Jacobs, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Claussen, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Hofmann-Apitius, Martin |e verfasserin |4 aut | |
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