Journal
JOURNAL OF NEUROCHEMISTRY
Volume 113, Issue 4, Pages 860-870Publisher
WILEY
DOI: 10.1111/j.1471-4159.2010.06658.x
Keywords
amyotrophic lateral sclerosis; antiapoptotic pathway; CSF; Cu; Zn superoxide dismutase; DJ-1; oxidative stress
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Funding
- Ministry of Health, Labour and Welfare of Japan
- Nakabayashi Trust For ALS Research
- ALS Foundation, Japan ALS Association
- Kanae Foundation for the Promotion of Medical Science
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P>Mutations in Cu/Zn superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (ALS), which could be attributed to the toxic properties of the misfolded protein, oxidative stress, and mitochondrial dysfunction. DJ-1 - a causative agent of familial Parkinson's disease PARK7 - is responsible for inducing antioxidative reaction. In this study, we showed the up-regulation of DJ-1 protein levels in mutant SOD1 transgenic mice through the lifespan were observed in the motor neurons. We demonstrated biochemically DJ-1 formed complexes with mutant SOD1 in the cell lysates. Furthermore, DJ-1 over-expression resulted in increased cell viability and reduced cell toxicity in mutant SOD1-transfected neuronal cells, because of improvement in apoptotic pathway and reduction in oxidative stress levels. We also evaluated DJ-1 levels in CSF collected from sporadic ALS patients and controls subjects. The CSF DJ-1 levels were significantly higher in patients with sporadic ALS than in control subjects. These results show that DJ-1 may be associated with sporadic and familial ALS pathogenesis. Therefore, insight into the effects of DJ-1 on mutant SOD1-mediated toxicity may provide a therapeutic advance for the treatment of motor neuron degeneration in ALS.
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