Mortiboys Heather
SITraN, Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, U.K.
Biochem Soc Trans. 2016 Dec 15;44(6):1617-1623. doi: 10.1042/BST20160242.
After the discovery of leucine-rich repeat kinase 2 (LRRK2) as a risk factor for sporadic Parkinson's disease (PD) and mutations in LRRK2 as a cause of some forms of familial PD, there has been substantial interest in finding chemical modulators of LRRK2 function. Most of the pathogenic mutations in LRRK2 are within the enzymatic cores of the protein; therefore, many screens have focused on finding chemical modulators of this enzymatic activity. There are alternative screening approaches that could be taken to investigate compounds that modulate LRRK2 cellular functions. These screens are more often phenotypic screens. The preparation for a screen has to be rigorous and enable high-throughput accurate assessment of a compound's activity. The pipeline to beginning a drug screen and some LRRK2 inhibitor and phenotypic screens will be discussed.
在富含亮氨酸重复激酶2（LRRK2）被发现是散发性帕金森病（PD）的一个风险因素，且LRRK2突变是某些形式的家族性PD的病因之后，人们对寻找LRRK2功能的化学调节剂产生了浓厚兴趣。LRRK2中的大多数致病突变位于该蛋白的酶核心区域内；因此，许多筛选都集中在寻找这种酶活性的化学调节剂上。还可以采用其他筛选方法来研究调节LRRK2细胞功能的化合物。这些筛选更多是表型筛选。筛选的准备工作必须严谨，以便能够对化合物的活性进行高通量准确评估。将讨论启动药物筛选的流程以及一些LRRK2抑制剂和表型筛选。
