Petrucelli Leonardo, Dawson Ted M
Mayo Clinic, Jacksonville, USA.
Ann Med. 2004;36(4):315-20. doi: 10.1080/07853890410031948.
Many neurodegenerative disorders such as Alzheimer's disease (AD) Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) are characterized by neuronal damage that may be caused by toxic, abnormal, aggregation-prone proteins. The purpose of this review is threefold: 1) to provide the reader with an overview of the genes involved in the abnormal processing and accumulation of misfolded proteins in neurodegenerative diseases using PD as a model disease; 2) to understand the cellular mechanisms for disposal of abnormal proteins, and the effects of toxic protein accumulation on ubiquitin proteasome system (UPS) and neuronal survival and 3) to discuss the development and challenges of cell culture and animal models for a rational and effective treatment for these disorders.
许多神经退行性疾病，如阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）和亨廷顿舞蹈病（HD），其特征是神经元损伤，这可能由有毒、异常、易于聚集的蛋白质引起。本综述的目的有三个：1）以PD作为模型疾病，向读者概述神经退行性疾病中与错误折叠蛋白的异常加工和积累相关的基因；2）了解处理异常蛋白质的细胞机制，以及有毒蛋白质积累对泛素蛋白酶体系统（UPS）和神经元存活的影响；3）讨论用于合理有效治疗这些疾病的细胞培养和动物模型的发展及挑战。
