Assays to evaluate biological pathways in Parkinsons disease

Parkin 可以去除受损的线粒体，从而保护神经元免于细胞死亡。然而，在家族性 PD 中，parkin 单倍体不足不能完全支持神经元存活。在 Michael J. Fox 基金会的部分资助下，并使用基因组编辑的神经元细胞系来监测 Parkin 的内源水平，我们进行了 qHTS 来识别 Parkin 位点的转录增强子。在第二种策略中，我们采用基于 α-突触核蛋白和富含亮氨酸重复激酶 2 (LRRK2) 的人类 PD 相关基因突变的秀丽隐杆线虫 (C. elegans) PD 酚类。使用激光扫描细胞术方法，我们正在开发一种与 384 孔 qHTS 兼容的线虫 PD 模型系统，用于评估研究药物和已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.