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首页> 外文期刊>The European Journal of Neuroscience >Akt is altered in an animal model of Huntington's disease and in patients.
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Akt is altered in an animal model of Huntington's disease and in patients.

机译：在亨廷顿舞蹈病的动物模型和患者中，Akt发生改变。

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The insulin-like growth factor I (IGF-1)/Akt pathway plays a crucial role in Huntington's disease by phosphorylating the causative protein, polyQ-huntingtin, and abolishing its toxic properties [Humbert et al. (2002)Dev. Cell, 2, 831-837; Rangone et al. (2004)Eur. J. Neurosci., 19, 273-279]. Therefore, dysregulation of this pathway may be essential for disease progression. In the present report, we thus aimed to analyse the status of Akt in brain or in peripheral tissues in Huntington's disease. Using a genetic model of Huntington's disease in rat that reproduces neuronal dysfunction and death, we show a progressive alteration of Akt during neuronal dysfunction and prior neurodegeneration. By analysing a limited number of lymphoblasts and lymphocytes, we detected modifications of Akt in Huntington's disease patients confirming a dysregulation of Akt in the disease process. Finally, we demonstrate that during late stages of the disease, Akt is cleaved into an inactive form by caspase-3. These observations demonstrate a progressive but marked alteration of this pro-survival pathway in Huntington's disease, and further implicate it as a key transduction pathway regulating the toxicity of huntingtin.
机译：胰岛素样生长因子I（IGF-1）/ Akt途径通过使病原蛋白polyQ-huntingtin磷酸化并消除其毒性而在亨廷顿舞蹈病中发挥关键作用[Humbert等。 （2002年）开发。电池，2，831-837; Rangone等。 （2004）Eur。 J. Neurosci。，19，273-279]。因此，该途径的失调对于疾病进展可能是必不可少的。因此，在本报告中，我们旨在分析亨廷顿氏病在大脑或外周组织中Akt的状态。使用大鼠亨廷顿舞蹈病的遗传模型，该模型可再现神经元功能障碍和死亡，我们显示了神经元功能障碍和先前的神经变性期间Akt的进行性改变。通过分析有限数量的淋巴母细胞和淋巴细胞，我们在亨廷顿舞蹈病患者中检测到Akt的修饰，证实了在疾病过程中Akt的失调。最后，我们证明了在疾病晚期，Akt被caspase-3切割成非活性形式。这些观察结果表明该促存活途径在亨廷顿舞蹈病中进行性但明显的改变，并且进一步暗示其为调节亨廷顿蛋白毒性的关键转导途径。

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