di Caudo Carla, Martínez-Valbuena Ivan, Mundiñano Iñaki-Carril, Gennetier Aurelie, Hernandez Maria, Carmona-Abellan Mar, Marcilla Garcia Irene, Kremer Eric J, Luquin Rosario
Division of Neuroscience, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.
Department of Neurology, Clinica Universidad de Navarra, Pamplona, Spain.
Front Mol Neurosci. 2020 Mar 25;13:49. doi: 10.3389/fnmol.2020.00049. eCollection 2020.
Parkinson's disease is characterized by motor and nonmotor symptoms that gradually appear as a consequence of the selective loss of dopaminergic neurons in the . Currently, no treatment can slow Parkinson's disease progression. Inasmuch, there is a need to develop animal models that can be used to understand the pathophysiological mechanisms underlying dopaminergic neuron death. The initial goal of this study was to determine if canine adenovirus type 2 (CAV-2) vectors are effective gene transfer tools in the monkey brain. A second objective was to explore the possibility of developing a large nonhuman primate that expresses one of the most common genetic mutations causing Parkinson's disease. Our studies demonstrate the neuronal tropism, retrograde transport, biodistribution, and efficacy of CAV-2 vectors expressing GFP and leucine-rich repeat kinase 2 (LRRK2) in the brain. Our data also suggest that following optimization CAV-2-mediated LRRK2 expression could help us model the neurodegenerative processes of this genetic subtype of Parkinson's disease in monkeys.
帕金森病的特征是运动和非运动症状，这些症状是由于黑质中多巴胺能神经元的选择性丧失而逐渐出现的。目前，没有治疗方法能够减缓帕金森病的进展。因此，需要开发可用于理解多巴胺能神经元死亡背后病理生理机制的动物模型。本研究的最初目标是确定2型犬腺病毒（CAV-2）载体是否是猴脑中有效的基因转移工具。第二个目标是探索培育出表达导致帕金森病的最常见基因突变之一的大型非人类灵长类动物的可能性。我们的研究证明了表达绿色荧光蛋白（GFP）和富含亮氨酸重复激酶2（LRRK2）的CAV-2载体在猴脑中的神经元嗜性、逆行运输、生物分布及效能。我们的数据还表明，经过优化后，CAV-2介导的LRRK2表达可能有助于我们在猴子身上模拟这种帕金森病基因亚型的神经退行性过程。
