| Autor: |
Chao Wang, Michael E. Ward, Robert Chen, Kai Liu, Tara E. Tracy, Xu Chen, Min Xie, Peter Dongmin Sohn, Connor Ludwig, Anke Meyer-Franke, Celeste M. Karch, Sheng Ding, Li Gan |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 9, Iss 4, Pp 1221-1233 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2017.08.019 |
| Popis: |
Lowering total tau levels is an attractive therapeutic strategy for Alzheimer's disease and other tauopathies. High-throughput screening in neurons derived from human induced pluripotent stem cells (iPSCs) is a powerful tool to identify tau-targeted therapeutics. However, such screens have been hampered by heterogeneous neuronal production, high cost and low yield, and multi-step differentiation procedures. We engineered an isogenic iPSC line that harbors an inducible neurogenin 2 transgene, a transcription factor that rapidly converts iPSCs to neurons, integrated at the AAVS1 locus. Using a simplified two-step protocol, we differentiated these iPSCs into cortical glutamatergic neurons with minimal well-to-well variability. We developed a robust high-content screening assay to identify tau-lowering compounds in LOPAC and identified adrenergic receptors agonists as a class of compounds that reduce endogenous human tau. These techniques enable the use of human neurons for high-throughput screening of drugs to treat neurodegenerative disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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