帕金森病动物模型的研究进展

Research advances in animal models of Parkinson disease

摘要:

帕金森病（PD）主要影响中枢神经系统的运动功能。PD的发病机制复杂，且缺乏有效的治疗方法，一直是神经科学的研究热点。近年来，PD的动物模型研究取得了显著进展。神经毒素模型可诱导多巴胺神经元损伤，常用于神经保护药物筛选，但未能完全重现PD的病理特征。转基因模型有助于发现潜在的治疗靶点，但缺乏多巴胺神经元的明显退化这一特征。组合模型可以产生更多样的运动和非运动症状，更全面地模拟PD病理过程。α突触核蛋白诱导模型能出现明显的病理蛋白聚集，更接近PD的典型病理表现。新兴模型可在体外重现PD病理特征，助力于个性化治疗的发展。越来越多的研究表明，PD更可能是一种综合征，非运动症状的研究逐渐受到重视。对PD非运动症状动物模型的研究有望在疾病早期发现生物标志物，并为严重非运动症状提供治疗方法。该文综述了各种PD动物模型的优势和局限性，为研究人员提供参考，帮助他们根据实验目的选择合适的模型。同时，该文旨在为深入理解PD发病机制和开发新的治疗方法提供理论支持。

Abstract:

Parkinson disease （PD） mainly affects the motor functions of the central nervous system， and due to its complex pathogenesis and a lack of effective therapies， it has always been a research hotspot in neuroscience. In recent years， significant progress has been made in the development of animal models for PD. Neurotoxin-induced models can cause dopaminergic neuronal injury and are often used for the screening of neuroprotective drugs， but they fail to fully represent the pathological features of PD. Transgenic models help to identify potential therapeutic targets， but with a lack of significant degeneration of dopaminergic neurons. Composite models can generate a wider range of motor and non-motor symptoms and comprehensively simulate the pathological process of PD. Models induced by α-synuclein can exhibit significant pathological protein aggregation， which closely resembles the typical pathological manifestations of PD. Emerging models can display the pathological features of PD in vitro and facilitate the development of individualized treatment. An increasing number of studies have shown that PD is more likely to be a syndrome， and the research on non-motor symptoms has gained more and more attention. Studies on animal models of non-motor symptoms have the potential to identify biomarkers in the early stage and provide therapies for severe non-motor symptoms. This article reviews the advantages and limitations of various animal models of PD， so as to provide a reference for researchers and help them select appropriate models based on experimental objectives. In addition， this article provides theoretical support for a deeper understanding of the pathogenesis of PD and the development of new therapies.