Reta Lila Weston Institute of Neurological Disease, Institute of Neurology, University College London, 1, Wakefield Street, WC1N 1PJ, UK.
Neurobiol Dis. 2009 Nov;36(2):393-400. doi: 10.1016/j.nbd.2009.08.011. Epub 2009 Aug 28.
Mutations in the DJ-1 gene have been linked with rare cases of early onset, autosomal recessive Parkinson's disease (PD). To determine whether DJ-1 is also involved in the pathogenesis of common forms of PD we have compared DJ-1 mRNA levels in a number of post-mortem PD and control brain regions using quantitative real-time PCR. Region-specific decreases were observed in DJ-1 mRNA levels in putamen, frontal cortex, parietal cortex and cerebellum in PD ( approximately 30-60%) compared to controls whilst an up-regulation was observed in the amygdala ( approximately 90%) and entorhinal cortex ( approximately 39%). Using quantitative western blot analysis, parallel decreases in DJ-1 protein levels were seen in frontal cortex, putamen and cerebellum of PD cases. By using 2-dimensional gel electrophoresis, we show preponderance of acidic pI isoforms of DJ-1 monomer in PD vulnerable regions, namely frontal cortex and medulla suggestive of differential post-translational modifications. Our findings point to a putative role of DJ-1 in the pathogenesis of PD.
DJ-1 基因突变与罕见的早发性常染色体隐性帕金森病（PD）有关。为了确定 DJ-1 是否也参与了常见形式的 PD 的发病机制，我们使用定量实时 PCR 比较了许多死后 PD 和对照脑区的 DJ-1 mRNA 水平。与对照组相比，PD 患者的纹状体、额叶皮质、顶叶皮质和小脑的 DJ-1 mRNA 水平观察到区域特异性降低（约 30-60%），而杏仁核（约 90%）和内嗅皮质（约 39%）观察到上调。使用定量 Western blot 分析，在 PD 病例的额叶皮质、纹状体和小脑观察到 DJ-1 蛋白水平的平行降低。通过使用 2 维凝胶电泳，我们显示 PD 易损区域（即额叶皮质和延髓）DJ-1 单体的酸性 pI 同种型占优势，提示存在差异的翻译后修饰。我们的发现表明 DJ-1 在 PD 的发病机制中可能具有作用。
