Genetic modifiers in a model tauopathy

tau蛋白病模型中的遗传修饰

• 批准号: G0600724/1
• 负责人: Michel Goedert
• 金额: $ 68.77万
• 依托单位: Medical Research Council
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600724%2F1
• 关键词: Genetic; modifiers; model; tauopathy

The formation of abnormal inclusions made of only a handful of proteins is believed to be central to the vast majority of cases of neurodegeneraive disease in man. Of these proteins, tau is implicated in a wide variety of diseases, including Alzheimer s disease, progressive supranuclear palsy, corticobasal degeneration, Pick s disease, argyrophilic grain disease and familial forms of frontotemporal dementia. The development of robust transgenic mouse models for these so-called tauopathies has made it possible to dissect the pathway leading from normal, soluble to abnormal, insoluble tau protein. We propose to identify proteins that modify (enhance or suppress) neurodegeneration in mouse models of human tauopathy. This may in turn lead to novel insights into possible prevention and treatment of these so far incurable diseases.

仅由少数蛋白质组成的异常包涵体的形成被认为是绝大多数人类神经退行性疾病病例的核心。在这些蛋白中，tau蛋白与多种疾病有关，包括阿尔茨海默病、进行性核上性麻痹、皮质基底变性、匹克病、嗜银性谷物病和家族性额颞叶痴呆。针对这些所谓的tau病的健壮的转基因小鼠模型的发展，使得剖析从正常的、可溶的tau蛋白到异常的、不可溶的tau蛋白的途径成为可能。我们建议在人类牛头病小鼠模型中鉴定改变（增强或抑制）神经变性的蛋白质。这可能反过来导致对这些迄今无法治愈的疾病的可能预防和治疗的新见解。