Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary Parkinsonism.

摘要: The hallmark of Parkinson's disease (PD) is the selective loss dopamine neurons in ventral midbrain. Although cause neurodegeneration PD unknown, a Mendelian inheritance pattern observed rare cases, indicating genetic factor. Furthermore, pathological analyses substantia nigra have correlated cellular oxidative stress and altered proteasomal function with PD. Homozygous mutations DJ-1 were recently described two families autosomal recessive Parkinsonism, one which large deletion that likely to lead function. Here we show embryonic stem cells deficient display increased sensitivity inhibition. accumulation reactive oxygen species toxin-treated DJ-1-deficient initially appears normal, but these are unable cope consequent damage ultimately leads apoptotic death. find derived from vitro–differentiated decreased survival stress. These data consistent protective role for DJ-1, demonstrate utility genetically modified cell–derived as models neuronal disorders.