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High Content Screening in Neurodegenerative Diseases
Published on: January 6, 2012
Differential DJ-1 gene expression in Parkinson's disease
Ravindran Kumaran1, Jana Vandrovcova, Connie Luk
1Reta Lila Weston Institute of Neurological Disease, Institute of Neurology, University College London, 1, Wakefield Street, WC1N 1PJ, UK.
Neurobiology of Disease
|September 1, 2009
Summary
Investigating the DJ-1 gene in Parkinson's disease (PD) revealed region-specific changes in its expression. DJ-1 levels decreased in key brain areas affected by PD, suggesting its involvement in the disease's common forms.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Mutations in the DJ-1 gene are associated with rare, early-onset, autosomal recessive Parkinson's disease (PD).
- The role of DJ-1 in the pathogenesis of common forms of PD remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of DJ-1 in the pathogenesis of common forms of Parkinson's disease.
- To compare DJ-1 mRNA and protein levels in post-mortem brain regions of PD patients and controls.
Main Methods:
- Quantitative real-time PCR to measure DJ-1 mRNA levels.
- Quantitative western blot analysis to assess DJ-1 protein levels.
- 2-dimensional gel electrophoresis to analyze DJ-1 post-translational modifications.
Main Results:
- Significant region-specific decreases in DJ-1 mRNA were observed in the putamen, frontal cortex, parietal cortex, and cerebellum of PD brains.
- DJ-1 mRNA levels were upregulated in the amygdala and entorhinal cortex of PD brains.
- DJ-1 protein levels showed parallel decreases in the frontal cortex, putamen, and cerebellum of PD cases.
- Differential post-translational modifications of DJ-1, indicated by a preponderance of acidic pI isoforms, were observed in PD-vulnerable regions.
Conclusions:
- The findings suggest a potential role for DJ-1 in the pathogenesis of common forms of Parkinson's disease.
- Altered DJ-1 expression and post-translational modifications may contribute to neurodegeneration in PD.
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