Yamashita Hiroshi, Matsumoto Masayasu
Hiroshima University, Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Hiroshima 734-8551, Japan.
Regen Med. 2007 Jul;2(4):447-55. doi: 10.2217/17460751.2.4.447.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by rigidity, bradykinesia, postural instability and resting tremor. The major symptoms are related to the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. The recent discovery of PARK genes causing familial forms of PD has led to a new approach in the study of the disease. The cause and pathogenesis of PD remains unknown; mitochondrial dysfunction, oxidative damage, endoplasmic reticulum stress, failure of the ubiquitin-proteasome system, environmental factors and genetic predisposition might all be involved. Toxin-induced PD animal models and genetic mouse models that mimic familial PD have contributed to investigating the molecular pathogenesis and treatment of the disease. Recently, neurogenesis in the striatum and subventricular zones in PD animal models have been reported. This review discusses molecular pathogenesis, experimental disease models and recent cell-based therapeutic approaches for PD.
帕金森病(PD)是一种进行性神经退行性疾病,其特征为僵硬、运动迟缓、姿势不稳和静止性震颤。主要症状与黑质致密部多巴胺能神经元的进行性丧失有关。最近发现导致家族性帕金森病的 PARK 基因,为该疾病的研究带来了新方法。帕金森病的病因和发病机制尚不清楚;线粒体功能障碍、氧化损伤、内质网应激、泛素-蛋白酶体系统功能衰竭、环境因素和遗传易感性可能都与之相关。毒素诱导的帕金森病动物模型和模拟家族性帕金森病的基因小鼠模型,有助于研究该疾病的分子发病机制和治疗方法。最近,有报道称帕金森病动物模型的纹状体和脑室下区存在神经发生。本文综述了帕金森病的分子发病机制、实验性疾病模型以及最近基于细胞的治疗方法。