National Neuroscience Institute, Singapore 308433, Singapore.
Department of Neurology, Singapore General Hospital, Singapore 169856, Singapore.
Int J Mol Sci. 2020 Apr 2;21(7):2464. doi: 10.3390/ijms21072464.
Parkinson's disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish, () , and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.
帕金森病（PD）是最常见的运动障碍疾病，具有运动和非运动症状。目前 PD 的治疗方案主要是对症治疗，因为其病因病理生理学尚未完全阐明。已经生成了多种动物模型来研究疾病的不同方面，以了解发病机制和治疗开发。该疾病模型可以通过神经毒素或基于遗传的方法在多种动物中生成，如非人类灵长类动物（NHP）、啮齿动物、斑马鱼、（）和果蝇。由于易于操作和适合大规模筛选试验，细胞疾病模型经常被使用。在神经毒素诱导的模型中，使用化学物质如 6-羟多巴胺（6-OHDA）、1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）、鱼藤酮和百草枯来重现疾病。PD 相关基因的遗传操作，如 α-突触核蛋白（SNCA）、富亮氨酸重复激酶 2（LRRK2）、Pten 诱导激酶 1（PINK1）、Parkin（PRKN）和蛋白去糖基化酶（DJ-1），用于转基因模型。已经生成了一种结合遗传和神经毒素方法的新兴模型，用于研究免疫系统在 PD 发病机制中的作用。在这里，我们讨论了不同 PD 模型的优缺点及其在不同研究目的中的实用性。
