以果蝇为模型研究泛酸激酶在帕金森疾病中的作用

帕金森氏症（PD）和人类泛酸激酶依赖型神经退行性疾病（PKAN）都为影响运动机能的神经退行性疾病。PKAN 的致病基因是人泛酸激酶 2（PANK2）基因，该基因编码辅酶A（Coenzyme A）合成通路中第一步反应的酶即泛酸激酶（Pantothenate kinase）。目前越来越多的研究表明PD也表现出辅酶A（Coenzyme A, CoA）代谢异常。我们前期研究发现果蝇PKAN模型（fbl果蝇）和PD模型pink1果蝇线粒体异常类似，而且Fbl过表达能有效拯救pink1果蝇的运动障碍，提示它们之间有密切联系。 基于此，我们计划以果蝇作为模式生物来研究PKAN 和PD 的关系，特别是研究Fbl和PINK1, Parkin关系，我们预期该研究将为PD发病机理及疾病的治疗提供重要新线索。

Parkinson’s disease (PD) and Pantothenate-Kinase-Associated Neurodegeneration (PKAN) are both movement disorders affecting basal gangalions. While PKAN is caused by mutations in PANK2, a mitochondrial pantothenate kinase (PANK) controlling CoA synthesis, emerging evidences also reveal defective CoA metabolism in PD. Our earlier studies have uncovered that fbl and pink1 flies exhibit similar mitochondrial defects and importantly, fbl overepression can effectively rescue pink1 movement defect, indicating an intimate relationship between them. On the basis of these, we plan in this proposal to continue this line of work, to study the relationship between PANK and PD, in particular PANK (fbl) and PINK1, Parkin. We anticipate this research will provide invaluable insights into the mechanism and even therapy design of PD.