Meredith Gloria E, Sonsalla Patricia K, Chesselet Marie-Francoise
Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Acta Neuropathol. 2008 Apr;115(4):385-98. doi: 10.1007/s00401-008-0350-x. Epub 2008 Feb 14.
Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is not understood. This disease occurs both sporadically and through inheritance of single genes, although the familial types are rare. Over the past decade or so, experimental and clinical data suggest that PD could be a multifactorial, neurodegenerative disease that involves strong interactions between the environment and genetic predisposition. Our understanding of the pathophysiology and motor deficits of the disease relies heavily on fundamental research on animal models and the last few years have seen an explosion of toxin-, inflammation-induced and genetically manipulated models. The insight gained from the use of such models has strongly advanced our understanding of the progression and stages of the disease. The models have also aided the development of novel therapies to improve symptomatic management, and they are critical for the development of neuroprotective strategies. This review critically evaluates these in vivo models and the roles they play in mimicking the progression of PD.
帕金森病(PD)是一种病因不明的进行性神经退行性疾病。这种疾病既散发出现,也可通过单基因遗传发生,尽管家族性类型较为罕见。在过去十年左右的时间里,实验和临床数据表明,PD可能是一种多因素神经退行性疾病,涉及环境与遗传易感性之间的强烈相互作用。我们对该疾病病理生理学和运动功能障碍的理解在很大程度上依赖于对动物模型的基础研究,并且在过去几年中,毒素诱导、炎症诱导和基因操纵模型大量涌现。使用这些模型所获得的见解极大地推进了我们对该疾病进展和阶段的理解。这些模型还有助于开发新的疗法以改善症状管理,并且它们对于神经保护策略的开发至关重要。本综述批判性地评估了这些体内模型及其在模拟PD进展中所起的作用。