Differential DJ-1 gene expression in Parkinson's disease

Neurobiol Dis. 2009 Nov;36(2):393-400. doi: 10.1016/j.nbd.2009.08.011. Epub 2009 Aug 28.

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 ( 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amygdala / metabolism
  • Cerebellum / metabolism
  • Entorhinal Cortex / metabolism
  • Female
  • Frontal Lobe / metabolism
  • Gene Expression Regulation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Oncogene Proteins / biosynthesis*
  • Oncogene Proteins / genetics*
  • Parietal Lobe / metabolism
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Protein Deglycase DJ-1
  • Putamen / metabolism
  • RNA, Messenger / biosynthesis
  • Up-Regulation / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • RNA, Messenger
  • PARK7 protein, human
  • Protein Deglycase DJ-1