Characterisation of candidate therapeutic targets for Huntington disease

亨廷顿病候选治疗靶点的表征

• 批准号: G0700090/1
• 负责人: Flaviano Giorgini
• 金额: $ 43.04万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0700090%2F1
• 关键词: Characterisation; candidate; therapeutic; targets; Huntington

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.

亨廷顿病是一种致命的遗传性疾病，其特征是大脑中形成病变。这是一种迟发性疾病，患者表现出不自主运动、僵硬和痴呆。尽管近年来大量的工作集中在这种疾病上，但目前还没有有效的治疗亨廷顿病的方法。面包酵母的遗传分析已被广泛用作研究遗传学和细胞过程的快速简便的方法。我们之前曾使用亨廷顿病的酵母模型来确定该疾病的候选治疗靶点，该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，我们建议验证哺乳动物细胞中酵母中发现的其他候选治疗靶点。此外，我们将使用酵母来表征已识别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机制的分子机制，并为这种疾病的新治疗方法提供信息。