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

自1997年以来，已在遗传性帕金森病（PD）变体中描述了11个基因（Park 1 -11）。对病理机制的深入了解最容易来自常染色体隐性形式，如Park 2/6/7，其中功能缺失突变可以启动发病机制。氧化途径最近被发现在公园2/6/7异常，和氧化应激是有据可查的晚发散发性PD脑。在我们最近合作鉴定丝氨酸苏氨酸激酶Pink 1为Park 6基因后，我们继续研究我们的Park 6家族的7个同胞（3名患者，3名携带者），他们都接受了皮肤和肌肉活检。我们计划进一步调查（一）黑质纹状体系统与其他神经元系统的影响，使用临床，电生理和成像技术，（II.）成淋巴细胞、成纤维细胞和肌肉中的氧化途径，（III.）Pink 1激酶和Pink 1相互作用蛋白的激活机制。这种方法将有助于更好地理解Pink 1在PD发病机制中的分子基础，并可能为旨在预防帕金森病神经退行性变的新型疗法定义靶分子。

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.