J. Neurochem. (2010) 113, 860–870.AbstractMutations 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.