帕金森病是遗传因素和环境因素共同作用的结果，黑质致密部多巴胺能神经元丢失，纹状体多巴胺耗竭是其典型的病理学特征。DJ-1基因的突变与常染色体隐性遗传的早发帕金森病及散发性帕金森病均有关系，它通过转录调节、抗氧化、分子伴侣和蛋白酶作用发挥神经保护作用，有可能成为PD新的治疗靶点。因此我们提出利用基因编辑技术（CRISPR-Cas）技术修复DJ-1基因，探索其对多巴胺神经元的保护作用及机制。通过CRISPR/Cas9实现外周血单核细胞DJ-1突变的定点修复，后经诱导成多巴胺能神经元，通过立体定向技术将诱导的多巴胺能神经元定点注入DJ-1基因敲除PD大鼠黑质中，分别在行为学、功能学、氧化、蛋白及基因水平检测DJ-I的修复正确与否、经诱导后多巴胺能神经元的活性以及移植前后黑质中多巴能胺神经元的数目与功能，探索恢复DJ-1功能对多巴胺能神经元可能的保护作用及机制。

Parkinson's disease is the result of genetic and environmental coefficient， Loss of nigrostriatal dopaminergic neurons and depletion of striatum dopamine are typical pathological changes. DJ-1 mutations is associated with autosomal-recessive PD with early onset, as well as sporadic PD. DJ-1 play neuroprotective effects via transcriptional regulation, antioxidant, chaperones and protease, which make it a new therapeutic target of PD. Our study use gene-editing technique (CRISPR-Cas, clustered regularly interspaced palindromic repeats) to repair the DJ-1 mutations in human peripheral blood monouclear cells and stereotactically injected into the substantia nigra of DJ-1 knockout PD rat after induced into dopaminergic neurons.To detect whether the repair of DJ-1 is correct, the activity of induced dopaminergic neurons, the number and function of nigrostriatal dopaminergic neurons before and after the transplantation from behavioral, function, oxidation, protein and gene levels, respectively. Our study aim to explore the protective effect of DJ-1 on dopaminergic neurons.