Xiong Yulan, Dawson Ted M, Dawson Valina L
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Adv Neurobiol. 2017;14:163-191. doi: 10.1007/978-3-319-49969-7_9.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic causes of Parkinson's disease (PD) and also one of the strongest genetic risk factors in sporadic PD. The LRRK2 protein contains a GTPase and a kinase domain and several protein-protein interaction domains. Both in vitro and in vivo assays in different model systems have provided tremendous insights into the molecular mechanisms underlying LRRK2-induced dopaminergic neurodegeneration. Among all the model systems, animal models are crucial tools to study the pathogenesis of human disease. How do the animal models recapitulate LRRK2-induced dopaminergic neuronal loss in human PD? To answer this question, this review focuses on the discussion of the animal models of LRRK2-associated PD including genetic- and viral-based models.
富含亮氨酸重复激酶2（LRRK2）基因的突变是帕金森病（PD）最常见的遗传病因，也是散发性PD中最强的遗传风险因素之一。LRRK2蛋白包含一个GTP酶和一个激酶结构域以及几个蛋白质-蛋白质相互作用结构域。在不同模型系统中进行的体外和体内试验，为LRRK2诱导多巴胺能神经变性的分子机制提供了深刻见解。在所有模型系统中，动物模型是研究人类疾病发病机制的关键工具。动物模型如何模拟LRRK2诱导的人类PD中多巴胺能神经元丢失？为回答这个问题，本综述重点讨论了与LRRK2相关的PD的动物模型，包括基于基因和病毒的模型。
