Department of Neurology, Yantai Yuhuangding Hospital of Medical College of Qingdao University, Yantai, Shandong, 264000, People's Republic of China,
J Mol Neurosci. 2013 Oct;51(2):539-49. doi: 10.1007/s12031-013-0022-8. Epub 2013 May 10.
Parkinson's disease (PD), which is estimated to affect approximately 1 % of the population over the age of 65, is the second most common neurodegenerative disorder after Alzheimer's disease. It was reported that pathogenic mutations in DJ-1 lead to autosomal recessive early-onset familial Parkinsonism. The L166P mutant of DJ-1 is the most commonly studied loss-of-function mutation in early onset familial PD, but the underlying mechanisms are still unknown. Edaravone is a powerful free radical scavenger used in clinical treatment for cerebral ischemic stroke. In the present study, we investigated the effects of edaravone on the neurotoxicity in PD-induced isoforms of DJ-1 containing the mutation L166P. Our results indicated that edaravone was able to significantly attenuate oxidative stress and improve mitochondrial function. Furthermore, edaravone was found to reduce apoptosis in Neuro2a cells through modulation of mitochondria-dependent apoptosis pathways. Interestingly, our result also demonstrated that edaravone was able to up-regulate VMAT2 expression in N2a cells in a dose-dependent manner. Our findings enhance the understanding of the neuro-protective effects of edaravone in cell models and suggest that edaravone offers significant protection in a PD-related in vitro model.
帕金森病（PD），估计影响 65 岁以上人群的 1%左右，是仅次于阿尔茨海默病的第二常见神经退行性疾病。有报道称 DJ-1 的致病突变导致常染色体隐性早发性家族性帕金森病。DJ-1 的 L166P 突变是研究最广泛的早发性家族性 PD 中丧失功能的突变，但潜在机制仍不清楚。依达拉奉是一种用于治疗脑缺血性中风的临床治疗的强大自由基清除剂。在本研究中，我们研究了依达拉奉对含有 L166P 突变的 DJ-1 同工型诱导的 PD 神经毒性的影响。结果表明，依达拉奉能够显著减轻氧化应激并改善线粒体功能。此外，通过调节线粒体依赖的凋亡途径，发现依达拉奉能够减少神经母细胞瘤（Neuro2a）细胞中的凋亡。有趣的是，我们的结果还表明，依达拉奉能够以剂量依赖的方式上调 Neuro2a 细胞中 VMAT2 的表达。我们的发现增强了对依达拉奉在细胞模型中神经保护作用的理解，并表明依达拉奉在 PD 相关的体外模型中提供了显著的保护。
