Modifiers of polyglutamine disease pathogenesis

亨廷顿吗?阿尔茨海默病（HD）是一种无法治愈的脑部疾病。它会导致异常运动、精神障碍（如抑郁症）和记忆问题。HD是一种遗传性疾病，患者的孩子中约有一半有患HD的风险。许多研究表明，有不同于原发性HD突变的遗传因素可以调节疾病的严重程度或发病年龄。该提案旨在描述动物模型中降低HD严重程度的遗传途径。这些基因和途径将用于优先考虑并最终选择可用于进一步研究的药物靶点，例如以开发可能的治疗方法为目的。我们将使用HD的小鼠和果蝇模型以及两种互补的遗传方法来识别这些修饰基因，这些方法使我们能够筛选这些修饰基因。这些筛选的后勤和筛选系统已在申请人持有的MRC赠款中建立。我们已经积累了大量的试点数据，这些数据表明这个项目可能会成功。这项研究将由David rubinszstein教授和Cahir O？Kane（剑桥大学）和Steve Brown教授（MRC哺乳动物遗传学单位，Harwell）。

Huntington?s disease (HD) is an incurable, disease affecting the brain. It results in abnormal movements, psychiatric disturbances (like depression) and memory problems. HD is a genetic disease and about half of the children of affected individuals are at-risk of developing the disease. A number of studies suggests that there are genetic factors distinct from the primary HD mutation that can modulate the severity of the disease or its age-at-onset. This proposal aims to characterise genetic pathways that reduce the severity of HD in animal models. These genes and pathways will be used to prioritise and eventually select druggable targets for further investigation, e.g. with the aim of developing possible therapies. We will identify such modifiers using mouse and fly models of HD and two complementary genetic approaches that allow us to screen for such modifier genes. The logistics and screening systems for these screens have been established in current MRC grants held by the applicants. We have accumulated a large amount of pilot data that show the likely success of this program. The research will be performed by Prof David Rubinsztein and Dr Cahir O?Kane (University of Cambridge) and Prof Steve Brown (MRC Mammalian Genetics Unit, Harwell).