Functional analysis of DJ-1, a causative gene for familial Parkinson's disease, and its pharmaceutical application

我们发现DJ-1通过与酪氨酸羟基酶、L多巴脱羧酶和VMAT-2直接相互作用并上调其基因表达，正向调节多巴胺的合成和分泌；DJ-1还正向调节线粒体复合体I的酶活性。此外，我们还分离了DJ-1结合化合物，用于修复帕金森病和卒中模型动物的运动缺陷和抑制神经细胞死亡。

We found that DJ-1 positively regulates synthesis and secretion of dopamine through direct interaction of DJ-1 with tyrosine hydroxylase, L-DOPA decarboxylase and VMAT-2 and through upregulation of their gene expression and that DJ-1 also positively regulates enzymatic activity of mitochondrial complex I. Furthermore, we isolated DJ-1-binding compounds that restored locomotion defect and inhibited neuronal cell death in Parkinson's disease and stroke model animals.