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DJ-1 deficiency in astrocytes selectively enhances mitochondrial Complex I inhibitor-induced neurotoxicity.


ABSTRACT: Parkinson's disease (PD) brains show evidence of mitochondrial respiratory Complex I deficiency, oxidative stress, and neuronal death. Complex I-inhibiting neurotoxins, such as the pesticide rotenone, cause neuronal death and parkinsonism in animal models. We have previously shown that DJ-1 over-expression in astrocytes augments their capacity to protect neurons against rotenone, that DJ-1 knock-down impairs astrocyte-mediated neuroprotection against rotenone, and that each process involves astrocyte-released factors. To further investigate the mechanism behind these findings, we developed a high-throughput, plate-based bioassay that can be used to assess how genetic manipulations in astrocytes affect their ability to protect co-cultured neurons. We used this bioassay to show that DJ-1 def

SUBMITTER: Mullett SJ 

PROVIDER: S-EPMC3076514 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature