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  4. A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism
 
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2022
Journal Article
Titel

A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism

Abstract
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.
Author(s)
Lage-Rupprecht, Vanessa
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Schultz, Bruce
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Dick, Justus
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Namysl, Marcin
Fraunhofer-Institut für Intelligente Analyse- und Informationssysteme IAIS
Zaliani, Andrea
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Gebel, Stephan
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Pless, Ole
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Reinshagen, Jeanette
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Ellinger, Bernhard
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Ebeling, Christian
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Esser, Alexander
Fraunhofer-Institut für Intelligente Analyse- und Informationssysteme IAIS
Jacobs, Marc
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Claussen, Carsten
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Hofmann-Apitius, Martin
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Zeitschrift
Patterns
Funder
Fraunhofer-Gesellschaft FhG
DOI
10.1016/j.patter.2021.100433
File(s)
N-648613.pdf (3.85 MB)
Language
English
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Fraunhofer-Institut für Intelligente Analyse- und Informationssysteme IAIS
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Tags
  • drug repurposing

  • knowledge graph

  • Alzheimer disease

  • tau phosphorylation

  • HDAC6

  • computational modelling, in vitro screening

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