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iPSC-derived neural cells for drug discovery of mitochondrial brain diseases

Speaker

Abstract

Mitochondrial defects represent a common pathogenetic mechanism associated with neurodegeneration. At the same time, mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Addressing the mechanisms underlying mitochondrial impairment in patient-derived neural cells may therefore lead to the identification of therapeutic strategies counteracting neurodegeneration.

A critical element for cell-based drug discovery is the use of cells that are homogeneous and obtainable in a reproducible manner. We recently showed that NPCs derived from human induced pluripotent stem cells (iPSCs) represent an effective model system for mtDNA disease drug discovery (Lorenz et al, Cell Stem Cell 2017). Here, we present how we derive NPCs and post-mitotic neurons in a robust manner in order to use these cells for therapeutic screenings. Finally, we describe how to analyze the mitochondrial and metabolic properties of the patient-derived cells and how to set up high-content analysis (HCA)-based compound screening strategies.

 


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iPSC-derived neural cells for drug discovery of mitochondrial brain diseases



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