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JOURNAL ARTICLE
REVIEW
[Calcineurin inhibitors and calcineurin-NFAT system].
Cyclosporin A and tacrolimus have been used as immunosuppressive agents initially in organ transplantation after their discovery, and are also used for treatment of the autoimmune disease, providing an excellent therapeutic effect. These agents act targeting on intracellular phosphatase calcineurin (CN), and subsequently inhibit activation of nuclear factor of activated T cells (NFAT), a key regulator of stimulation-dependent gene activation. The CN-NFAT system is involved not only in the immunoregulation including activation and development of helper T cells, regulatory T cells and NKT cells, but in a variety of cellular and developmental events other than immune system. CN inhibitors also affect organs outside of immune system leading to adverse effects, including nephrotoxicity and glucose intolerance. We review recent findings in CN-NFAT system, as well as development of potential CN inhibitors.
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