a-突触核蛋白磷酸化在帕金森病（PD）发病机制中发挥重要作用。然而，PD 中主要调控a-突触核蛋白磷酸化的关键激酶尚不明确。我们前期研究发现PD患者脑区a-突触核蛋白磷酸化特异性激酶polo-like kinases(PLKs)表达水平异常升高，且其与a-突触核蛋白的过度磷酸化水平呈正相关。因此，我们推测PLKs在PD中对a-突触核蛋白磷酸化起重要调控作用，调节PLKs水平/活性可以有效调控a-突触核蛋白磷酸化水平，进而对神经元起到保护作用。本研究将通过调节PLKs的表达水平或激酶活性，检测PLKs对a-突触核蛋白磷酸化水平及细胞活力的影响，研究PLKs与a-突触核蛋白之间的相互作用，比较不同PLKs对a-突触核蛋白磷酸化及其下游通路的影响，分析不同PLKs生成的磷酸化a-突触核蛋白对小鼠多巴胺能神经元的影响，进而探讨PLKs在PD发病机制中的作用，为PD防治的新药开发提供理论依据。

a-Synuclein phosphorylation plays a key role in the pathogenesis of Parkinson's disease (PD). However, it is unclear which kinase(s) control the a-synuclein phosphorylation in PD. In our previous studies, we found polo-like kinases(PLKs), a specific a-synuclein phosphorylation related kinase family, significantly increased in PD brains compared with controls; moreover, the increased PLKs were positively correlated with the hyperphosphorylation of a-synuclein over the course of PD. Therefore, we propose that changing the levels and/or kinase activity of PLKs could effectively regulate a-synuclein phosphorylation, and further protect neurons. In this project, the levels or kinase activity of PLKs would be changed by transfection or administration of PLKs inhibitors, phosphorylation of a-synuclein and cell viability would be assessed among different groups; then the interaction between PLKs and a-synuclein in neurons would be investigated; furthermore, a-synuclein phosphorylation related down-stream pathways would be analyzed among different PLK groups; finally, the effects of different PLK members induced phosphorylated a-synuclein to dopaminergic neuron in mouse model would be determined to figure out the roles of PLKs in the pathogenesis of PD and may open a new way to develop therapeutic strategy for PD.