Reference - Detail
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 |
PII | JNC6658 |
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 | 4.066 |
Times Cited | 20 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY NEUROSCIENCES |
Resource | |
Human and Animal Cells | NB2a(RCB2639) |