auy-954 and Disease-Models--Animal

Future treatments of multiple sclerosis (MS), a chronic autoimmune neurodegenerative disease of the central nervous system (CNS), aim for simultaneous early targeting of peripheral immune function and neuroinflammation. Sphingosine-1-phosphate (S1P) receptor modulators are among the most promising drugs with both "immunological" and "non-immunological" actions. Selective S1P receptor modulators have been recently approved for MS and shown clinical efficacy in its mouse model, the experimental autoimmune encephalomyelitis (EAE). Here, we investigated the anti-inflammatory/neuroprotective effects of ozanimod (RPC1063), a S1P

Topics: Animals; Anti-Inflammatory Agents; beta-Alanine; Cell Line; Central Nervous System; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Glutamates; Indans; Interleukin-1beta; Mice, Inbred C57BL; Microglia; Multiple Sclerosis; Neostriatum; Oxadiazoles; RNA, Messenger; Sphingosine-1-Phosphate Receptors; Synapses; Synaptic Transmission; T-Lymphocytes; Thiophenes

Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system and an animal model of human inflammatory demyelinating polyradiculoneuropathy. AUY954, which targets selectively the sphingosine-1-phosphate receptor 1 (S1P(1)), is known to sequester lymphocytes into secondary lymphoid tissues. In EAN rats, AUY954 greatly prevented paraparesis if administrated from the day of immunization. T cell, B cell, and macrophage infiltration, inflammatory demyelination, and local expression of interleukine-17 and matrix metalloproteinase-9 in sciatic nerves of EAN rats were significantly decreased by AUY954 treatment. Therefore, S1P(1) modulation might be a potential treatment option for inflammatory neuropathies.

Topics: Animals; B-Lymphocytes; beta-Alanine; Chemotaxis, Leukocyte; Disease Models, Animal; Guillain-Barre Syndrome; Immunologic Factors; Interleukin-17; Macrophages; Male; Matrix Metalloproteinase 9; Neuritis, Autoimmune, Experimental; Paraparesis; Rats; Rats, Inbred Lew; Receptors, Lysosphingolipid; Sciatic Nerve; T-Lymphocytes; Thiophenes; Treatment Outcome