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帕金森病的实验动物模型:从评估症状学到α-突触核蛋白靶向疾病修饰的转变

Experimental animal models of Parkinson's disease: A transition from assessing symptomatology to α-synuclein targeted disease modification.

作者信息

Ko Wai Kin D, Bezard Erwan

机构信息

Motac Neuroscience Ltd, Manchester, United Kingdom.

Motac Neuroscience Ltd, Manchester, United Kingdom; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.

出版信息

Exp Neurol. 2017 Dec;298(Pt B):172-179. doi: 10.1016/j.expneurol.2017.07.020. Epub 2017 Jul 29.

DOI:10.1016/j.expneurol.2017.07.020
PMID:28764902
Abstract

With the understanding that α-synuclein plays a major role in the pathogenesis of Parkinson's disease (PD), novel animal models have been developed for conducting preclinical research in screening novel disease modifying therapies. Advancements in research techniques in α-synuclein targeted disease modification have utilised methods such as viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy Bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration. In applying these cutting-edge research tools with sophisticated trial designs in preclinical drug trials, a useful platform has emerged for developing candidate agents with disease modifying actions, promising a greater chance of success for clinical translation. In this article, we describe the transition of well-established animal models of PD symptomatology to newly developed models of PD pathogenesis, with specific focus on methods of viral-mediated and inoculation of pathogenic α-synuclein, that aim to aid scientific translation of neuroprotective strategies.

摘要

鉴于α-突触核蛋白在帕金森病(PD)发病机制中起主要作用,已开发出新型动物模型用于开展临床前研究,以筛选新型疾病修饰疗法。α-突触核蛋白靶向疾病修饰研究技术的进展利用了诸如病毒介导的人α-突触核蛋白表达以及接种来自PD患者路易小体的致病性α-突触核蛋白物种等方法,以准确模拟进行性自我传播的神经退行性变。在临床前药物试验中应用这些具有先进试验设计的前沿研究工具时,已出现了一个用于开发具有疾病修饰作用的候选药物的有用平台,有望为临床转化带来更大的成功机会。在本文中,我们描述了从成熟的PD症状学动物模型到新开发的PD发病机制模型的转变,特别关注病毒介导和接种致病性α-突触核蛋白的方法,旨在促进神经保护策略的科学转化。

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