Sci. Signal., 22 October 2013
Overcoming a Myelination Maturity BlockDemyelinating diseases, such as multiple sclerosis (MS), are characterized by the failure of oligodendrocytes to mature and produce myelin, the protective sheaths surrounding axons. The role of the orphan G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor GPR17 in this process is debated. Hennen et al. identified a GPR17-selective small-molecule agonist and showed that application of this agonist induced G protein–mediated signaling that prevented maturation of cultured oligodendrocytes. The findings establish an inhibitory role for GPR17 in the cellular maturation process that enables remyelination of injured axons and suggest that GPR17 may be pharmacologically targeted to treat MS.
Citation: S. Hennen, H. Wang, L. Peters, N. Merten, K. Simon, A. Spinrath, S. Blättermann, R. Akkari, R. Schrage, R. Schröder, D. Schulz, C. Vermeiren, K. Zimmermann, S. Kehraus, C. Drewke, A. Pfeifer, G. M. König, K. Mohr, M. Gillard, C. E. Müller, Q. R. Lu, J. Gomeza, E. Kostenis, Decoding Signaling and Function of the Orphan G Protein–Coupled Receptor GPR17 with a Small-Molecule Agonist. Sci. Signal. 6, ra93 (2013).
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