DJ-1可保护细胞抵抗氧化应激的攻击，其下降被认为与氧化应激损伤和帕金森病（PD）发病有关。家族性PD患者中DJ-1基因突变可导致DJ-1易被蛋白酶体所降解，散发性PD患者中黑质部DJ-1也有下降，但机制不明，了解其异常机制可帮助阐明散发性PD患者的发病机制。我们前期研究发现hsa-miR-4639-5p可调控DJ-1的表达， PD患者外周血中hsa-miR-4639-5p水平较正常对照显著升高，且其异常增高主要来源于中枢神经系统的改变，与DJ-1水平下降有关，但hsa-miR-4639-5p异常上调的原因仍不明确。我们将从miRNA的表达调控入手，通过研究明确hsa-miR-4639-5p的启动子和上游调节因子，在此基础上观察PD病理状态下hsa-miR-4639-5p调控异常与DJ-1水平异常降低、氧化应激异常增加和多巴胺能神经元变性死亡间的关系，以期帮助阐释散发性PD发生的分子机制。

DJ-1 protein protects cells against oxidative stress. DJ-1 deficiency plays a crucial role in oxidative insult and Parkinson's disease (PD) pathogenesis. In familial PD, mutations of DJ-1 gene can cause instability of the protein which makes DJ-1 easily degraded by proteasome. Reduced DJ-1 protein level has also been reported in substantia nigra of sporadic PD patients, but the mechanism is unclear. Our previous study showed that DJ-1 gene is post-transcriptionally regulated by hsa-miR-4639-5p. Plasma miR-4639-5p level was identified to be significantly up-regulated in PD patients compared to healthy controls. Moreover, abnormal up-regulated plasma miR-4639-5p was derived from exosomes, which reflects pathological changes in the central nervous system, relating to abnormal decreased DJ-1 protein level, but the underlying mechanism is still obscure. In this proposal, we are going to identify the promoter region and the regulatory elements of hsa-miR-4639-5p. Based on the results, we will continuously investigate the abnormal regulation of hsa-miR-4639-5p expression in pathological conditions of PD. All these will help us to understand the molecular mechanism underlying DJ-1 deficiency, burst of oxidative stress and neuronal death in PD.