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

我们发现DJ-1通过与酪氨酸羟化酶、L-DOPA脱羧酶和VMAT-2的直接相互作用以及通过上调它们的基因表达来正调节多巴胺的合成和分泌，并且DJ-1还正调节线粒体复合物I的酶活性。此外，我们分离出DJ-1结合的化合物，其恢复帕金森病和中风模型动物的运动缺陷并抑制神经元细胞死亡。

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.