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

多年来，我们一直对氧化应激与DJ-1（隐性帕金森病的罕见病因）之间的关系感兴趣，并重点关注氧化应激与线粒体定位之间的关系。在当前阶段，我们已经探索了DJ-1缺乏对小鼠和大鼠大脑的影响。我们发现DJ-1的缺失改变了细胞信号通路，从而在细胞水平上导致代谢酶变化的积累。

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.