[Therapeutic strategy against multiple sclerosis].
The pathogenesis of multiple sclerosis (MS) remains to be elucidated and there is no curative therapy against MS, though we have several disease modifying drugs. In this symposium. I introduce several new strategies against development of autoimmune processes and axonal degeneration in MS. Several mechanisms regulate immune system not to attack self components. One of the most potent regulatory cells is CD4 + CD25 + FoxP + regulatory T cells (Treg), which suppress development of both T helper 1 and 2. Thus, to increase the number and function of Treg is an approach to suppress autoimmune diseases. We have found recently that midkine suppresses the development of Treg. and that suppression of midkine by RNA aptamer alleviates symptoms of experimental autoimmune encephalomyetitis, an animal model of MS. by expanding Treg. Another important strategy against MS is to suppress axonal degeneration which reportedly occurs from an early stage of MS. We have found that the most toxic agent from activated macrophages and microglia is glutamate that was produced by glutaminase and released through gap-junction. Thus, inhibitor for glutaminase and gap-junction may be other candidates to treat MS. Interferon-beta also effectively suppress glutamate production by these cells and subsequently suppress development of axonal degeneration.
Suzumura
Akio
A
Department of Neuroimmunology, RIEM, Nagoya University.
D000818:Animals; D052157:Aptamers, Nucleotide / Q000627:therapeutic use; D015551:Autoimmunity; D001369:Axons / Q000473:pathology; D016207:Cytokines / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D017629:Gap Junctions; D018698:Glutamic Acid / Q000378:metabolism; D005972:Glutaminase / Q000037:antagonists & inhibitors; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D000078792:Midkine; D009103:Multiple Sclerosis / Q000209:etiology* / Q000628:therapy*; D009410:Nerve Degeneration; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells; D018418:Th2 Cells
D052157:Aptamers, Nucleotide; D016207:Cytokines; D004791:Enzyme Inhibitors; D000078792:Midkine; D018698:Glutamic Acid; D016899:Interferon-beta; D005972:Glutaminase