Assays to evaluate biological pathways in Parkinsons disease

帕金去除了受损的线粒体，线粒体保护神经元免受细胞死亡。然而，作为家族性帕金森病的一种形式，Parkin单倍体功能不全不能完全支持神经元存活。利用迈克尔·J·福克斯基金会的部分资金，并使用基因组编辑的神经细胞系来监测Parkin的内源性水平，我们进行了一项qHTS，以确定Parkin基因的转录增强子。在第二种策略中，我们使用秀丽线虫(C.elegans)PD表型，基于人PD相关基因突变的α-突触核蛋白和富含亮氨酸的重复蛋白激酶2(LRRK2)。利用激光扫描细胞术方法，我们正在开发一个384孔qHTS兼容的线虫PD模型系统，用于评估研究药物和批准的药物抑制线虫神经退化的能力。

Parkin removes damaged mitochondria, which protects neurons from cell death. However, in a form of familial PD, parkin haploinsufficiency cannot fully support neuronal survival. With funding in part from the Michael J. Fox Foundation and using a genome-edited neuronal cell line to monitor the endogenous levels of Parkin, we conducted a qHTS to identify transcriptional enhancers of the parkin locus. In a second strategy, we are employing a Caenorhabditis elegans (C. elegans) PD phenolog based on human PD-linked gene mutations in alpha-synuclein and the leucine-rich repeat kinase 2 (LRRK2). Using laser scanning cytometry methods, we are developing a 384-well qHTS-compatible C. elegans PD model system for evaluating libraries of investigational agents and approved drugs for their ability to inhibit nematode neurodegeneration.