pyrimidinones and myelin-oligodendrocyte-glycoprotein-(35-55)

Multiple sclerosis (MS) is an autoimmune chronic disease of the central nervous system (CNS) characterized by immune-mediated inflammation, demyelination and subsequent axonal damage. Gene expression profiling showed that Nurr1, an orphan nuclear receptor, is down-regulated in peripheral blood mononuclear cells of MS patients. Nurr1 exerts an anti-inflammatory role repressing the activity of the pro-inflammatory transcription factor NF-kB. Here, we report that the preventive treatment with isoxazolo-pyridinone 7e, an activator of Nurr1 signaling pathway, reduces the incidence and the severity of a MS murine model, i.e. experimental autoimmune encephalomyelitis (EAE). The compound is able to attenuate inflammation and neurodegeneration in spinal cords of EAE mice by an NF-kB pathway-dependent process.

Topics: Animals; Axons; Cell Count; Demyelinating Diseases; Down-Regulation; Encephalomyelitis, Autoimmune, Experimental; Female; Isoxazoles; Macrophages; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; NF-kappa B; Nuclear Receptor Subfamily 4, Group A, Member 2; Oxazoles; Peptide Fragments; Pyrimidinones; Signal Transduction; Spinal Cord; T-Lymphocytes