Olig2-Targeted G-Protein-Coupled Receptor Gpr17 Regulates Oligodendrocyte Survival in Response to Lysolecithin-Induced Demyelination.
Ou Z, Sun Y, Lin L, You N, Liu X, Li H, Ma Y, Cao L, Han Y, Liu M, Deng Y, Yao L, Lu QR, Chen Y.
J Neurosci. 2016 Oct 12;36(41):10560-10573
Uracil nucleotide/cysteinyl leukotriene receptor is a G protein-coupled receptor that in humans is encoded by GPR17.
GPR17 is highly expressed in certain precursors of oligodendrocytes in the nerve tissue of the (CNS); it is overexpressed in CNS tissues experiencing demyelination injuries; within 48 hours of the latter types of injuries, GPR17 expression is induced in dying neurons within and on the borders of injury, in infiltrating microglia and macrophages, and in activated oligodendrocyte precursor cells.
Studies focusing on nerve tissue indicate that GPR17 is: a) highly expressed in precursors to mature oligodendrocytes but not expressed in mature oligodendrocytes, suggesting that GPR17 must be down-regulated in order for precursor cells to proceed to terminal oligodendrocyte differentiation; b) activated by uridine, Uridine diphosphate (UDP) andUDP-glucose to stimulate outward K+ channels and the aforementioned maturation responses in oligodenrocyte precursor cells; c) also activated by LTC4 and LTD4; d) more highly expressed in (CNS) tissues of animal models undergoing EAE and focal demyelination as well as in the CNS tissues of humans in MS; e) expressed in injured neurons and acts to reduce the extent of spinal cord injury f) acts to elevate neurogenesis.
Studies suggest that GPR17 is a sensor of damage in the CNS and participates in the resolution of this damage by clearing and/or promoting the re-myelination of injured neurons caused by a variety of insults perhaps including old age.
Pranlukast is a cysteinyl leukotriene receptor-1 antagonist. This drug works similarly tos montelukast (Singulair). These have a function the antagonism of bronchospasm caused, principally in asthmatics, by an allergic reaction to accidentally or inadvertently encountered allergens.
Will this make it... We can add it to the increasing list of potential remyelination drugs.