The spreading of misfolded alpha-synuclein (α-syn) protein has been observed in animal models of Parkinson’s disease (PD) and other α-synucleinopathies that mimic human PD pathologies. In animal models, the spreading of α-syn has been associated with motor dysfunction and neuronal death. However, variability in both susceptible brain regions and cellular populations limits our understanding of the consequences of α-syn spreading and the development of associated therapies. Here, we have reviewed the physiological and pathological functions of α-syn and summarized the susceptible brain regions and cell types identified from human postmortem studies and exogenous α-syn injection-based animal models. We have reviewed the methods for inducing α-syn aggregation, the specific hosts, the inoculation sites, the routes of propagation, and other experimental settings that may affect the spreading pattern of α-syn, as reported in current studies. Understanding the spread of α-syn to produce a consistent PD animal model is vital for future drug discovery.

在帕金森病 (PD) 和其他模拟人类 PD 病理的 α-突触核蛋白病的动物模型中观察到了错误折叠的 α-突触核蛋白 (α-syn) 蛋白的扩散。在动物模型中，α-syn 的传播与运动功能障碍和神经元死亡有关。然而，易感脑区和细胞群的变异性限制了我们对 α-syn 传播后果和相关疗法发展的理解。在这里，我们回顾了 α-syn 的生理和病理功能，并总结了从人类死后研究和基于外源性 α-syn 注射的动物模型中确定的易感脑区和细胞类型。我们回顾了诱导 α-syn 聚集的方法、特定宿主、接种位点、传播途径，和其他可能影响 α-syn 传播模式的实验设置，如当前研究报告的那样。了解 α-syn 的传播以产生一致的 PD 动物模型对于未来的药物发现至关重要。