帕金森病（Parkinson's disease，PD）属于神经退行性疾病，在中老年人中发病率较高。目前研究认为，帕金森病的发生与线粒体功能失调及ROS积累相关。Trx2是定位于线粒体中负责ROS清除的硫氧还蛋白。在前期工作中，我们发现Trx2在模式生物斑马鱼的脑部有非常高的表达。随后，利用Morpholino技术在斑马鱼中进行Trx2敲低实验，我们发现出现PD相关表型，该表型类似于遗传性PD致病基因Pink1在斑马鱼中敲低的表型。因此在本课题中，我们将利用golden talen技术建立稳定的Trx2敲除品系，分析PD相关表型，分析氧化压力，药物和年龄因素对该品系PD诱发的影响。其次，根据我们的工作基础和已报道的二者功能分析，我们认为Pink1可能对Trx2进行磷酸化修饰。我们将探讨Pink1与Trx2在帕金森病诱发中的关系。该课题的研究将为预防和治疗帕金森病提供新的思路和方向。

Parkinson's disease (PD) belongs to the chronic neurodegenerative diseases, which has a high incidence in old people. To date, it has been demonstrated that the mitochondria dysfunction and the accumulated ROS account for the pathogenesis of PD. Trx2 is one member of Trxs family, which locates in mitochondria and is responsible for the ROS scavenging. In our preliminary study, we found that Trx2 had a high expression in the brain of zebrafish. By injection with morpholino (MO), we further found that the Trx2 morphants showed a phenotype same as the Pink1 morphants reported before. It has been reported that Pink1 mutations are responsible for recessive inherited PD. Meanwhile，Trx2 knockdown in zebrafish led to reduced ΔΨm and ROS accumulation. In this proposal, we will generate the Trx2 homozygous and heterozygous null zebrafish lines by the golden-talen technology. Utilizing the knock-out zebrafish strains, we will determine the role of Trx2 dysfunction in the pathogenesis of PD. We also assess how the oxidative stress and drugs play a role in the induction of PD and the aging factor will also be explored .The second aim in our study is to explore the relevance between Trx2 and Pink1 in the pathogenesis of PD. Because of the reported data of their function and our preliminary study, we infer that Trx2 may be phosphorylated by Pink1. The results from this proposal will provide reliable and innovated theoretical basis for PD therapeutic treatment.