RRC ID 38204
Author Yamashita S, Mori A, Kimura E, Mita S, Maeda Y, Hirano T, Uchino M.
Title DJ-1 forms complexes with mutant SOD1 and ameliorates its toxicity.
Journal J Neurochem
Abstract 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.
Volume 113(4)
Pages 860-70
Published 2010-5-1
DOI 10.1111/j.1471-4159.2010.06658.x
PMID 20202083
MeSH Aged Amyotrophic Lateral Sclerosis / genetics Amyotrophic Lateral Sclerosis / metabolism* Amyotrophic Lateral Sclerosis / physiopathology Animals Apoptosis / physiology Cell Survival / physiology Cells, Cultured Female Humans Macromolecular Substances / metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Middle Aged Motor Neurons / metabolism Nerve Degeneration / genetics Nerve Degeneration / metabolism Nerve Degeneration / physiopathology Oncogene Proteins / cerebrospinal fluid Oncogene Proteins / genetics Oncogene Proteins / metabolism* Oxidative Stress / physiology Peroxiredoxins Protein Binding / physiology Protein Deglycase DJ-1 Superoxide Dismutase / genetics Superoxide Dismutase / metabolism* Superoxide Dismutase-1 Up-Regulation / physiology
IF 4.87
Times Cited 20
Human and Animal Cells