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

DJ-1最近被证明与家族性帕金森病（PD） PARK7的发病有关。DJ-1已被证明在转录调控和抗氧化应激中发挥作用，其功能的丧失被认为是PD发病的诱因。本研究将重组DJ-1蛋白注入左侧黑质6-羟基多巴胺（6-OHDA）的PD模型大鼠脑中。野生型DJ-1显著改善PD表型，包括黑质和纹状体多巴胺能神经元死亡、纹状体多巴胺和多巴胺转运体水平下降以及运动异常，而L166P DJ-1 （PD患者中发现的一种突变型DJ-1）则没有显著改善。此外，加入重组DJ-1可以抑制SH-SY5Y细胞中活性氧的产生和6-OHDA诱导的细胞死亡。这些发现表明，DJ-1是帕金森病的治疗靶点。

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.