Towards an Understanding of GPR17 Signaling in Remyelination

GPR17 is a clinical stage drug target for the treatment of demyelinating diseases. Despite significant interest in GPR17, understanding of how GPR17 targeted drug therapies modulate cellular functions to promote remyelination is limited. In this thesis, we show that different GPR17 antagonists regulate signalling from the receptor in different ways. We also develop methods for measuring differentiation of oligodendrocytes. In these experiments, GPR17 antagonists also displayed differences in how they modulated differentiation. Altogether, these findings reveal previously unknown aspects of GPR17 pharmacology and signalling, with potential relevance for therapeutic efficacy of GPR17 antagonists.