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

自1997年以来，已有11个基因(park1-11)在遗传性帕金森氏病(PD)变种中被发现。对病理机制的了解应该最容易从Park2/6/7这样的常染色体隐性形式中获得，在这些形式中，功能突变的丧失可以启动发病机制。最近在Park2/6/7中发现了氧化途径的异常，而氧化应激在晚发型散发性帕金森病脑中被很好地记录下来。在我们最近合作确认丝氨酸苏氨酸激酶PINK1是Park6基因之后，我们继续研究我们的Park6家族，有7个同胞(3名患者，3名携带者)，他们已经符合皮肤和肌肉活组织检查。我们计划进一步调查(I)使用临床、电生理和成像技术比较黑质纹状体系统与其他神经系统的影响，(Ii)淋巴母细胞、成纤维细胞和肌肉中的氧化途径(III)PINK1激酶和PINK1相互作用蛋白的激活机制这一方法将有助于更好地了解PINK1功能在帕金森病发病机制中的分子基础，并可能为旨在防止帕金森病神经变性的新疗法确定靶分子。

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.