UNASSIGNED: One of the causes of @entity2319 in chronic @entity15 @entity1 is the inability of oligodendrocyte progenitor cells (OPCs) to terminate their maturation program at lesions. To identify key regulators of myelin gene expression acting at the last stages of OPC maturation we developed a drug repositioning strategy based on the @entity19 immortalized oligodendrocyte (OL) cell line Oli-neu brought to the premyelination stage by stably expressing a key factor regulating the last stages of OL maturation. The Prestwick Chemical Library   of 1,200 FDA-approved compound(s) was repositioned at three dosages based on the induction of @entity2610 ( @entity2610 ) expression. Drug hits were further validated using dosage-dependent reproducibility tests and biochemical assays. The glucocorticoid class of compounds was the most highly represented and we found that they can be divided in three groups according to their efficacy on @entity2610 up-regulation. Since target identification is crucial before bringing compounds to the clinic, we searched for common targets of the primary screen hits based on their known chemical-target interactomes, and the pathways predicted by top ranking compounds were validated using specific inhibitors. Two of the top ranking compounds, @entity69576 and @entity6914 , act as @entity2751 ( @entity2751 ) agonists to up-regulate myelin gene expression in the Oli-neuM cell line. Further, RxRy activation is required for @entity2610 expression upon @entity69576 and @entity6914 treatment. These data indicate @entity6914 and @entity69576 as potential promyelinating drugs and also provide a mechanistic understanding of their mode of action in the pathway leading to myelination in OPCs. Furthermore, our classification of glucocorticoids with respect to @entity2610 expression provides important novel insights into their effects in the CNS and a rational criteria for their choice in combinatorial therapies in de-myelinating diseases.

@entity6914 and XXXX Act as @entity2751 Agonists to Promote Myelin Gene Expression and RxRy Receptor Activation.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity2610 :: ('4155', 'Gene') :: ['MBP', 'Myelin Basic Protein'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity2751 :: ('6608', 'Gene') :: ['Smoothened', 'Smo'] @entity2319 :: ('MESH:D003638', 'Disease') :: ['permanent disability'] @entity69576 :: ('MESH:D006206', 'Chemical') :: ['Halcinonide'] @entity6914 :: ('MESH:D002990', 'Chemical') :: ['Clobetasol'] @entity15 :: ('MESH:D009103', 'Disease') :: ['multiple sclerosis']
@entity69576 :: (MESH:D006206,Chemical) :: ['Halcinonide']
