Functional analysis of DJ-1, a causative gene product for familial Parkinson's disease

DJ-1最近已被证明是负责家族性帕金森病（PD），PARK 7的发病。DJ-1已被证明在转录调节和抗氧化应激中发挥作用，并且其功能的丧失被认为触发PD的发作。在本研究中，将重组DJ-1蛋白质施用到已经在左侧黑质中注射6-羟基多巴胺（6-OHDA）的PD模型大鼠的脑中。PD表型，包括黑质和纹状体中的多巴胺能神经元死亡，纹状体中多巴胺和多巴胺转运蛋白水平降低以及运动异常，通过野生型DJ-1而不是L166 P DJ-1（在PD患者中发现的DJ-1的突变形式）显著改善。此外，通过添加重组DJ-1抑制了SH-SY 5 Y细胞中由6-OHDA诱导的活性氧簇的产生和细胞死亡。这些发现表明DJ-1是PD的治疗靶点。

DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. DJ-1 has been shown to play roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD. In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra. PD phenotypes, including dopaminergic neuron death both in the substantia nigra and striatum, decrease in dopamine and dopamine transporter levels in the striatum, and motor abnormality, were dramatically improved by wild-type DJ-1 but not L166P DJ-1, a mutant form of DJ-1 found in PD patients. Furthermore, production of reactive oxygen species and cell death induced by 6-OHDA in SH-SY5Y cells were inhibited by addition of the recombinant DJ-1. These findings suggest that DJ-1 is a therapeutic target for PD.