Name
Title | ||
|---|---|---|
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. |
Year | DOI | Venue |
|---|---|---|
2022 | 10.1016/j.patter.2021.100433 | Patterns |
Keywords | DocType | Volume |
drug repurposing,Alzheimer disease,HDAC6,tau phosphorylation,knowledge graph,data integration,computational modeling,in vitro screening | Journal | 3 |
Issue | ISSN | Citations |
3 | 2666-3899 | 0 |
PageRank | References | Authors |
0.34 | 0 | 14 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Vanessa Lage-Rupprecht | 1 | 0 | 0.68 |
| Bruce Schultz | 2 | 0 | 0.68 |
| Justus Dick | 3 | 0 | 0.34 |
| Marcin Namysl | 4 | 0 | 0.68 |
| Andrea Zaliani | 5 | 0 | 0.34 |
| Stephan Gebel | 6 | 0 | 0.34 |
| Ole Pless | 7 | 0 | 0.34 |
| Jeanette Reinshagen | 8 | 0 | 0.34 |
| Bernhard Ellinger | 9 | 0 | 0.34 |
| Christian Ebeling | 10 | 0 | 0.34 |
| Alexander Esser | 11 | 0 | 0.34 |
| Marc Jacobs | 12 | 1 | 1.06 |
| Carsten Claussen | 13 | 0 | 0.34 |
| Martin Hofmann-Apitius | 14 | 0 | 0.34 |