Abstract
Alzheimer’s disease is a complex disorder encompassing multiple pathological features with associated genetic and molecular culprits. However, target-based therapeutic strategies have so far proved ineffective. The aim of this study is to develop a methodology harnessing the transcriptional changes associated with Alzheimer’s disease to develop a high content quantitative disease phenotype that can be used to repurpose existing drugs. Firstly, the Alzheimer’s disease gene expression landscape covering severe disease stage, early pathology progression, cognitive decline and animal models of the disease has been defined and used to select a set of 153 drugs tending to oppose disease-associated changes in the context of immortalised human cancer cell lines. The selected compounds have then been assayed in the more biologically relevant setting of iPSC-derived cortical neuron cultures. It is shown that 51 of the drugs drive expression changes consistently opposite to those seen in Alzheimer’s disease. It is hoped that the iPSC profiles will serve as a useful resource for drug repositioning within the context of neurodegenerative disease and potentially aid in generating novel multi-targeted therapeutic strategies.
Original language | English |
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Article number | 220 |
Journal | Translational psychiatry |
Volume | 9 |
Issue number | 1 |
Early online date | 6 Sept 2019 |
DOIs | |
Publication status | Published - 2019 |