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Methods for assessing the role of calcineurin immunosuppression and neurotoxicity

机译:评估钙调神经磷酸酶免疫抑制作用和神经毒性作用的方法

摘要

The present invention relates to a method of identifying drugs or agents which have immuno-suppressive effects through or as a result of their effect on calcineurin, including drugs which affect the calcineurin A&agr; (CNA&agr;) subunit or the calcineurin A&bgr; (CNA&bgr;) subunit. In addition, the present invention relates to a method of identifying drugs which reduce (partially or totally) phosphorylation of the microtubule-associated protein tau, in the nervous system of a mammal; a method of identifying drugs which reduce (partially or totally) paired helical filament formation in the nervous system of a mammal; and a method of identifying drugs which reduce (partially or totally) formation of paired helical filaments, amyloid deposits or both. The present invention also relates to transgenic non-human mammals, such as rodents and particularly mice, which lack a functional calcineurin gene and, thus, have disyrupted calcineurin expression.
机译:本发明涉及鉴定通过钙调神经磷酸酶或由于其对钙调神经磷酸酶的作用而具有免疫抑制作用的药物或试剂的方法,所述药物或试剂包括影响钙调神经磷酸酶A&agr的药物。 (CNA&agr;)亚基或钙调神经磷酸酶A&bgr; (CNA&bgr;)子单位。另外,本发明涉及鉴定在哺乳动物的神经系统中减少(部分或全部)微管相关蛋白tau磷酸化的药物的方法。鉴定减少(部分或全部)哺乳动物神经系统中成对的螺旋丝形成的药物的方法;以及鉴定减少(部分或全部)成对的螺旋丝,淀粉样蛋白沉积物或两者的形成的药物的方法。本发明还涉及缺乏功能性钙调神经磷酸酶基因并因此破坏了钙调神经磷酸酶表达的转基因非人类哺乳动物,例如啮齿动物,特别是小鼠。

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