AUY954, a selective S1P(1) modulator, prevents experimental autoimmune neuritis.

Abstract

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.

• Authors: Zhi-Yuan Zhang, Zhiren Zhang, Caroline Zug, Barbara Nuesslein-Hildesheim, David Leppert, Hermann J Schluesener
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 216 Issue 1-2 Pg. 59-65 (Nov 30 2009) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 19804913 (Publication Type: Journal Article)

Chemical References

• AUY 954
• Immunologic Factors
• Interleukin-17
• Receptors, Lysosphingolipid
• Thiophenes
• beta-Alanine
• Matrix Metalloproteinase 9

Topics

• Animals
• B-Lymphocytes (drug effects, immunology)
• Chemotaxis, Leukocyte (drug effects, immunology)
• Disease Models, Animal
• Guillain-Barre Syndrome (drug therapy, immunology, metabolism)
• Immunologic Factors (pharmacology, therapeutic use)
• Interleukin-17 (metabolism)
• Macrophages (drug effects, immunology)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Neuritis, Autoimmune, Experimental (drug therapy, immunology, metabolism)
• Paraparesis (drug therapy, immunology, prevention & control)
• Rats
• Rats, Inbred Lew
• Receptors, Lysosphingolipid (drug effects, metabolism)
• Sciatic Nerve (drug effects, immunology, metabolism)
• T-Lymphocytes (drug effects, immunology)
• Thiophenes (pharmacology, therapeutic use)
• Treatment Outcome
• beta-Alanine (analogs & derivatives, pharmacology, therapeutic use)