Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Curr Neuropharmacol. 2023;21(5):1241-1272. doi: 10.2174/1570159X21666230216101659.
Parkinson's disease (PD) is a debilitating neurodegenerative multisystem disorder leading to motor and non-motor symptoms in millions of individuals. Despite intense research, there is still no cure, and early disease biomarkers are lacking. Animal models of PD have been inspired by basic elements of its pathogenesis, such as dopamine dysfunction, alpha-synuclein accumulation, neuroinflammation and disruption of protein degradation, and these have been crucial for a deeper understanding of the mechanisms of pathology, the identification of biomarkers, and evaluation of novel therapies. Imaging biomarkers are non-invasive tools to assess disease progression and response to therapies; their discovery and validation have been an active field of translational research. Here, we highlight different considerations of animal models of PD that can be applied to future research, in terms of their suitability to answer different research questions. We provide the reader with important considerations of the best choice of model to use based on the disease features of each model, including issues related to different species. In addition, positron emission tomography studies conducted in PD animal models in the last 5 years are presented. With a variety of different species, interventions and genetic information, the choice of the most appropriate model to answer research questions can be daunting, especially since no single model recapitulates all aspects of this complex disorder. Appropriate animal models in conjunction with in vivo molecular imaging tools, if selected properly, can be a powerful combination for the assessment of novel therapies and developing tools for early diagnosis.
帕金森病（PD）是一种使人衰弱的神经退行性多系统疾病，导致数百万人出现运动和非运动症状。尽管进行了深入研究，但仍没有治愈方法，而且缺乏早期疾病生物标志物。PD 的动物模型是基于其发病机制的基本要素而设计的，例如多巴胺功能障碍、α-突触核蛋白积累、神经炎症和蛋白质降解紊乱，这些对于深入了解病理学机制、确定生物标志物以及评估新疗法至关重要。成像生物标志物是评估疾病进展和治疗反应的非侵入性工具；它们的发现和验证一直是转化研究的活跃领域。在这里，我们强调了 PD 动物模型的不同考虑因素，这些因素可以应用于未来的研究，以满足不同研究问题的需求。我们为读者提供了基于每个模型的疾病特征，包括与不同物种相关的问题，选择最合适模型的重要考虑因素。此外，还介绍了过去 5 年在 PD 动物模型中进行的正电子发射断层扫描研究。由于有各种不同的物种、干预措施和遗传信息，选择最合适的模型来回答研究问题可能具有挑战性，特别是因为没有单一的模型可以再现这种复杂疾病的所有方面。如果选择得当，适当的动物模型与体内分子成像工具相结合，可以成为评估新疗法和开发早期诊断工具的强大组合。
