Assays to evaluate biological pathways in Parkinsons disease

帕金移除受损的线粒体，线粒体保护神经元免于细胞死亡。然而，在家族性PD的一种形式中，帕金单倍不足不能完全支持神经元存活。在迈克尔·J·福克斯基金会的部分资助下，我们使用基因组编辑的神经元细胞系来监测帕金的内源性水平，进行了qHTS来鉴定帕金基因座的转录增强子。在第二种策略中，我们采用秀丽隐杆线虫（C. elegans）PD phenolog，其基于α-突触核蛋白和富含亮氨酸的重复激酶2（LRRK 2）中的人类PD连锁基因突变。利用激光扫描细胞仪的方法，我们正在开发一个384孔的qHTS兼容的C。elegans PD模型系统，用于评估研究药物和批准药物库抑制线虫神经变性的能力。

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.