Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neuron. 2010 Jun 10;66(5):646-61. doi: 10.1016/j.neuron.2010.04.034.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the degeneration of dopamine (DA) and non-DA neurons, the almost uniform presence of Lewy bodies, and motor deficits. Although the majority of PD is sporadic, specific genetic defects in rare familial cases have provided unique insights into the pathogenesis of PD. Through the creation of animal and cellular models of mutations in LRRK2 and alpha-synuclein, which are linked to autosomal-dominant PD, and mutations in parkin, DJ-1, and PINK1, which are responsible for autosomal-recessive PD, insight into the molecular mechanisms of this disorder are leading to new ideas about the pathogenesis of PD. In this review, we discuss the animal models for these genetic causes of PD, their limitations, and value. Moreover, we discuss future directions and potential strategies for optimization of the genetic models.
帕金森病(PD)是一种进行性神经退行性疾病,其特征是多巴胺(DA)和非-DA 神经元的退化,Lewy 体的几乎普遍存在,以及运动缺陷。尽管大多数 PD 是散发性的,但在罕见的家族性病例中特定的遗传缺陷为 PD 的发病机制提供了独特的见解。通过创建与常染色体显性 PD 相关的 LRRK2 和 alpha-synuclein 突变、与常染色体隐性 PD 相关的 parkin、DJ-1 和 PINK1 突变的动物和细胞模型,深入了解该疾病的分子机制正在为 PD 的发病机制提供新的思路。在这篇综述中,我们讨论了这些 PD 遗传病因的动物模型,及其局限性和价值。此外,我们还讨论了遗传模型优化的未来方向和潜在策略。