DJ-1 function and oxidative stress (Inter-lab project)

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We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. In the current period, we have explored the effects of DJ-1 deficiency in the brains of mice and rats. We find that loss of DJ-1 alters cellular signaling pathways that result, at a cellular level, in the accumulation of changes in metabolic enyzmes. As part of this collaborative project, we have crossed DJ-1 and NQO1 deficient animals, both of which have been shown previously to have protective effects against oxidative damage in parkinsonian-related in vitro or in vivo models. We have a completed large set of behavioral assays in the double homozygote animals and see modest phenotypes. Brains have also been taken for post-mortem analysis. We have also made a new strain of DJ-1 knockout rats using CRISPR/Cas9 in the Sprague-Dawley outbred background. After aging these animals, we expect to be able to confirm or refute whether there is spontaneous neurodegeneration. These animals are housed as an aging cohort and may have some behavioral phenotypes that still need to be confirmed.