Lasbleiz Christelle, Mestre-Francés Nadine, Devau Gina, Luquin Maria-Rosario, Tenenbaum Liliane, Kremer Eric J, Verdier Jean-Michel
MMDN, University of Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier, France.
Department of Neurology, Clinica Universidad de Navarra, Pamplona, Spain.
Front Mol Neurosci. 2019 Feb 11;12:10. doi: 10.3389/fnmol.2019.00010. eCollection 2019.
Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration of L-dopa and deep brain stimulation are potent therapies, their costs, side effects and gradual loss of efficacy underlines the need to develop other approaches. Unfortunately, the lack of pertinent animal models that reproduce DA neuron loss and behavior deficits-in a timeline that mimics PD progression-has hindered the identification of alternative therapies. A complementary approach to transgenic animals is the use of nonhuman primates (NHPs) combined with the overexpression of disease-related genes using viral vectors. This approach may induce phenotypes that are not influenced by developmental compensation mechanisms, and that take into account the personality of animals. In this review article, we discuss the combination of gene transfer and NHPs to develop "genetic" models of PD that are suitable for testing therapeutic approaches.
帕金森病（PD）是一种进行性中枢神经系统疾病，主要与运动功能受损有关。PD的发展历经数十年，与纹状体多巴胺传递逐渐减少以及黑质致密部（SNpc）中多巴胺能（DA）神经元的丧失有关。虽然左旋多巴的给药和深部脑刺激是有效的治疗方法，但它们的成本、副作用以及疗效的逐渐丧失凸显了开发其他方法的必要性。不幸的是，缺乏在模拟PD进展的时间线内再现DA神经元丧失和行为缺陷的相关动物模型，阻碍了替代疗法的识别。与转基因动物互补的方法是使用非人类灵长类动物（NHPs）并结合使用病毒载体过表达疾病相关基因。这种方法可能会诱导不受发育补偿机制影响且考虑到动物个性的表型。在这篇综述文章中，我们讨论基因转移与NHPs的结合，以开发适用于测试治疗方法的PD“遗传”模型。
