Differential DJ-1 gene expression in Parkinson's disease

Abstract

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 (∼ 30–60%) compared to controls whilst an up-regulation was observed in the amygdala (∼ 90%) and entorhinal cortex (∼ 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.