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Kv1.3 potassium channels as a therapeutic target in multiple sclerosis.

机译:Kv1.3钾通道作为多发性硬化症的治疗靶标。

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摘要

We discuss the potential use of inhibitors of Kv1.3 potassium channels in T lymphocytes as therapeutics for multiple sclerosis. Current treatment strategies target the immune system in a non-selective manner. The resulting general immunosuppression, toxic side-effects and increased risk of opportunistic infections create the need for more selective therapeutics. Autoreactive effector-memory T (T(EM)) cells, considered to be major mediators of autoimmunity, express large numbers of Kv1.3 channels. Selective blockers of Kv1.3 inhibit calcium signaling, cytokine production and proliferation of T(EM) cells in vitro, and T(EM) cell-motility in vivo. Kv1.3 blockers ameliorate disease in animal models of multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus and contact dermatitis without compromising the protective immune response to acute infections. Kv1.3 blockers have a good safety profile in rodents and primates.
机译:我们讨论了在T淋巴细胞中Kv1.3钾通道抑制剂作为多发性硬化症治疗剂的潜在用途。当前的治疗策略以非选择性方式靶向免疫系统。由此产生的一般免疫抑制,毒性副作用和机会性感染的风险增加,因此需要更选择性的治疗方法。自身反应性效应记忆T细胞(T(EM))被认为是自身免疫的主要介质,可表达大量Kv1.3通道。 Kv1.3的选择性阻滞剂在体外抑制T(EM)细胞的钙信号传导,细胞因子产生和增殖,在体内抑制T(EM)细胞的运动。 Kv1.3阻滞剂可改善多发性硬化症,类风湿性关节炎,1型糖尿病和接触性皮炎的动物模型中的疾病,而不会损害对急性感染的保护性免疫反应。 Kv1.3阻滞剂在啮齿动物和灵长类动物中具有良好的安全性。

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