Characterisation of candidate therapeutic targets for Huntington disease

亨廷顿病是一种致命的遗传性疾病，其特征是在大脑中形成病变。这是一种迟发性疾病，患者表现为不自主运动、僵硬和痴呆。虽然近年来对这种疾病进行了大量的研究，但目前还没有有效的治疗方法。面包酵母的遗传分析作为一种快速简便的研究遗传和细胞过程的方法已被广泛使用。我们之前使用了亨廷顿病的酵母模型来确定该疾病的候选治疗靶点，最近在亨廷顿病小鼠模型的临床前试验中得到了验证。在这里，我们建议在哺乳动物细胞中验证酵母中确定的其他候选治疗靶点。此外，我们将使用酵母来表征鉴定的修饰剂之间的遗传相互作用。最终，我们认为这项工作将阐明亨廷顿病发病的分子机制，并为这种疾病的新治疗方法提供信息。

Huntington disease is a fatal hereditary disorder that is characterised by the formation of lesions in the brain. It is a late onset disease in which patients exhibit involuntary movements, rigidity, and dementia. Though a great amount of work has been focused on this disease in recent years, no effective therapy is yet available for Huntington disease. Genetic analysis in bakers yeast has been used extensively as a fast and easy approach to study genetics and cellular processes. We have previously used a yeast model of Huntington disease to identify a candidate therapeutic target for this disease, which has recently been validated in preclinical trials in a mouse model of Huntington disease. Here, we propose to validate additional candidate therapeutic targets identified in yeast in mammalian cells. In addition, we will use yeast to characterise the genetic interactions among the identified modifiers. Ultimately, we feel this work will elucidate the molecular mechanisms of pathogenesis in Huntington disease as well as inform novel therapeutic approaches for this disorder.