Le Weidong, Sayana Pavani, Jankovic Joseph
1st Affiliated Hospital, Dalian Medical University, Dalian, 116011, China,
Neurotherapeutics. 2014 Jan;11(1):92-110. doi: 10.1007/s13311-013-0234-1.
Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.
帕金森病（PD）是一种病因不明的进行性神经退行性疾病，尽管环境因素和遗传因素之间的复杂相互作用被认为是特定神经元丢失的致病机制。通过对动物模型的研究，可能会更好地理解该疾病过程的病因、发病机制和分子机制。虽然细胞和组织模型有助于阐明相关的分子途径，但动物模型更适合研究发病机制和潜在的治疗策略。与帕金森病最相关的动物模型包括那些由选择性破坏儿茶酚胺能系统的神经毒性化学物质诱导产生的模型，如6-羟基多巴胺；1-甲基-1,2,3,6-四氢吡啶；农业农药毒素，如鱼藤酮和百草枯；泛素蛋白酶体系统抑制剂；炎症调节剂；以及几种基因操作模型，如α-突触核蛋白、DJ-1、PINK1、帕金和富含亮氨酸重复激酶2转基因或基因敲除动物。遗传和非遗传动物模型都有其独特的优点和局限性，在用于研究发病机制或治疗方法时必须加以考虑。本综述对目前用于测试新型治疗策略的各种帕金森病体内模型的知识进行了总结和批判性回顾。
