The Park6 from of idiopathic Parkinson`s disease: Characterization of patients, their cells, and functional role of Pink1 kinase

特发性帕金森病的 Park6：患者及其细胞的特征以及 Pink1 激酶的功能作用

• 批准号: 5446392
• 负责人: Professor Dr. Georg Auburger
• 金额: --
• 依托单位: Klinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5446392?language=en
• 关键词: Park6; idiopathic; Parkinson; disease; Characterization

Eleven genes (Park1-11) have been described in hereditary Parkinson`s disease (PD) variants since 1997. Insight into the mechanisms of pathology should come easiest from autosomal recessive forms like Park2/6/7, where loss of function mutations can initiate pathogenesis. Oxidative pathways have recently been found abnormal in Park2/6/7, and oxidative stress is well documented in late onset sporadic PD brains. After our recent collaborative identification of the serine threonine kinase Pink1 as the Park6 gene, we continue to study our Park6 family with 7 sibs (3 patients, 3 carriers), who have been compliant with skin and muscle biopsies. We plan to further investigate (I.) the affection of the nigrostriatal system versus other neuronal systems using clinical, electrophysiological, and imaging techniques, (II.) oxidative pathways in lymphoblasts, fibroblasts and muscle, (III.) mechanisms of activation of Pink1 kinase and Pink1-interacting proteins. This approach will help to better understand the molecular basis of Pink1 functions in the pathogenesis of PD and possibly define target molecules for novel therapies aimed to prevent neurodegeneration in Parkinson`s disease.

自 1997 年以来，已有 11 个基因 (Park1-11) 在遗传性帕金森病 (PD) 变异中被描述。对病理机制的深入了解应该最容易从常染色体隐性形式（如 Park2/6/7）中获得，其中功能缺失突变可能引发发病。最近发现 Park2/6/7 的氧化途径异常，并且氧化应激在晚发散发性 PD 大脑中得到充分记录。在我们最近合作将丝氨酸苏氨酸激酶 Pink1 鉴定为 Park6 基因后，我们继续研究 Park6 家族的 7 名同胞（3 名患者，3 名携带者），他们已接受了皮肤和肌肉活检。我们计划使用临床、电生理学和成像技术进一步研究 (I.) 黑质纹状体系统相对于其他神经元系统的影响，(II.) 淋巴母细胞、成纤维细胞和肌肉中的氧化途径，(III.) Pink1 的激活机制激酶和 Pink1 相互作用蛋白。这种方法将有助于更好地了解 Pink1 在 PD 发病机制中功能的分子基础，并可能为旨在预防帕金森病神经退行性变的新疗法定义靶分子。