Abstract
High-throughput phenotypic screening enables the identification of new therapeutic targets even when the molecular mechanism underlying the disease is unknown. In the case of neurodegenerative disease, there is a dire need to identify new targets that can ameliorate, halt, or reverse degeneration. Stem cell-based disease models are particularly powerful tools for phenotypic screening because they use the same cell type affected in patients. Here, we describe the expansion of mouse stem cells and human induced pluripotent stem cells as well as the differentiation of these cells into neural lineages that, when exposed to neuroinflammatory stress, can be used for compound screening followed by hit identification, validation, and target deconvolution.
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Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft, EU Joint Programme–Neurodegenerative Disease Research, the Bundesministerium für Bildung und Forschung, and the Max Planck Society. J.B., M.G., and L.M. are supported by fellowships from the Hans and Ilse Breuer Stiftung. We thank Tanya Levin for editing the manuscript.
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Abo-Rady, M. et al. (2019). Phenotypic Screening Using Mouse and Human Stem Cell-Based Models of Neuroinflammation and Gene Expression Analysis to Study Drug Responses. In: Ziegler, S., Waldmann, H. (eds) Systems Chemical Biology. Methods in Molecular Biology, vol 1888. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8891-4_2
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DOI: https://doi.org/10.1007/978-1-4939-8891-4_2
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