Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Int J Mol Sci. 2020 Mar 13;21(6):1961. doi: 10.3390/ijms21061961.
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, but various non-motor symptoms (NMS) often precede motor symptoms. Recently, NMS have attracted much attention as a clue for identifying patients in a prodromal stage of PD, which is an excellent point at which to administer disease-modifying therapies (DMTs). These prodromal symptoms include olfactory loss, constipation, and sleep disorders, especially rapid eye movement sleep behavior disorder (RBD), all of which are also important for elucidating the mechanisms of the initiation and progression of the disease. For the development of DMTs, an animal model that reproduces the prodromal stage of PD is also needed. There have been various mammalian models reported, including toxin-based, genetic, and alpha synuclein propagation models. In this article, we review the animal models that exhibit NMS as prodromal symptoms and also discuss an appropriate prodromal model and its importance for the development of DMT of PD.
帕金森病（PD）的特征是黑质中多巴胺能神经元的丧失和随后的运动症状，但各种非运动症状（NMS）常常先于运动症状出现。最近，NMS 作为识别 PD 前驱期患者的线索引起了广泛关注，这是给予疾病修饰疗法（DMT）的绝佳时机。这些前驱症状包括嗅觉丧失、便秘和睡眠障碍，特别是快速眼动睡眠行为障碍（RBD），这些都是阐明疾病发生和进展机制的重要因素。为了开发 DMT，还需要一种能够再现 PD 前驱期的动物模型。已经报道了各种哺乳动物模型，包括基于毒素、遗传和α-突触核蛋白传播的模型。在本文中，我们综述了表现出 NMS 作为前驱症状的动物模型，并讨论了合适的前驱模型及其对 PD 的 DMT 开发的重要性。
