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

多年来，我们一直对氧化应激与DJ-1（一种罕见的隐性帕金森病病因）之间的关系感兴趣，并专注于氧化应激与线粒体定位之间的关系。在当前阶段，我们探索了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传导途径，从而在细胞水平上导致代谢酶变化的积累。 作为该合作项目的一部分，我们已经将DJ-1和NQO 1缺陷动物进行了交叉，这两种动物之前都已被证明在帕金森病相关的体外或体内模型中对氧化损伤具有保护作用。我们在双纯合子动物中进行了一系列完整的行为测定，并观察到适度的表型。大脑也被用于死后分析。 我们还在Sprague-Dawley远交背景中使用CRISPR/Cas9制备了DJ-1敲除大鼠的新品系。 在这些动物老化后，我们期望能够证实或反驳是否存在自发性神经退行性变。这些动物作为老化队列圈养，可能具有一些仍需确认的行为表型。

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.