The G Protein‐Coupled Receptor GPR17: Overview and Update

Abstract The GPR17 receptor is a G protein‐coupled receptor (GPCR) that seems to respond to two unrelated families of endogenous ligands: nucleotide sugars (UDP, UDP‐galactose, and UDP‐glucose) and cysteinyl leukotrienes (LTD 4 , LTC 4 , and LTE 4 ), with significant affinity at micromolar and nanomolar concentrations, respectively. This receptor has a broad distribution at the level of the central nervous system (CNS) and is found in neurons and in a subset of oligodendrocyte precursor cells (OPCs). Unfortunately, disparate results emerging from different laboratories have resulted in a lack of clarity with regard to the role of GPR17‐targeting ligands in OPC differentiation and in myelination. GPR17 is also highly expressed in organs typically undergoing ischemic damage and has various roles in specific phases of adaptations that follow a stroke. Under such conditions, GPR17 plays a crucial role; in fact, its inhibition decreases the progression of ischemic damage. This review summarizes some important features of this receptor that could be a novel therapeutic target for the treatment of demyelinating diseases and for repairing traumatic injury.