Department of Neurological Surgery, University of California San Francisco, 1855 Folsom Street, San Francisco, CA, USA.
Neurotherapeutics. 2013 Jul;10(3):498-510. doi: 10.1007/s13311-013-0191-8.
Protein aggregation as a result of misfolding is a common theme underlying neurodegenerative diseases. Accordingly, most recent studies aim to prevent protein misfolding and/or aggregation as a strategy to treat these pathologies. For instance, state-of-the-art approaches, such as silencing protein overexpression by means of RNA interference, are being tested with positive outcomes in preclinical models of animals overexpressing the corresponding protein. Therapies designed to treat central nervous system diseases should provide accurate delivery of the therapeutic agent and long-term or chronic expression by means of a nontoxic delivery vehicle. After several years of technical advances and optimization, gene therapy emerges as a promising approach able to fulfill those requirements. In this review we will summarize the latest improvements achieved in gene therapy for central nervous system diseases associated with protein misfolding (e.g., amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, Huntington's, and prion diseases), as well as the most recent approaches in this field to treat these pathologies.
蛋白质错误折叠导致的聚集是神经退行性疾病的一个常见主题。因此，最近的大多数研究旨在预防蛋白质错误折叠和/或聚集，以此作为治疗这些疾病的策略。例如，通过 RNA 干扰来沉默蛋白质过表达的最先进方法，在过度表达相应蛋白质的动物临床前模型中得到了积极的结果。旨在治疗中枢神经系统疾病的疗法应该通过无毒的输送载体提供治疗剂的准确输送和长期或慢性表达。经过多年的技术进步和优化，基因治疗作为一种有前途的方法出现，能够满足这些要求。在这篇综述中，我们将总结与蛋白质错误折叠相关的中枢神经系统疾病的基因治疗的最新进展（例如肌萎缩侧索硬化症、阿尔茨海默病、帕金森病、亨廷顿病和朊病毒病），以及该领域治疗这些疾病的最新方法。
