National Center for Global Health, Istituto Superiore di Sanita, Rome, Italy.
National Center for Drug Research and Evaluation, Istituto Superiore di Sanita, Rome, Italy.
Curr Gene Ther. 2017;17(5):327-363. doi: 10.2174/1566523218666180119120726.
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and prion disease are not timely and effectively treated using conventional therapies. This emphasizes the need for alternative therapeutic approaches. In this respect, gene-based therapies have been adopted as potentially feasible alternative therapies, where the microRNA (miRNA) approach has experienced a great explosion in recent years. Because miRNAs have been shown to be implicated in the pathogenesis of several diseases including neurodegenerative diseases, they are intensely studied as candidates for diagnostic and prognostic biomarkers, as predictors of drug response and as therapeutic agents. In this review, we evaluate the feasibility of both direct and indirect miRNA mimics and inhibitors toward the regulation of neurodegenerative-related genes both in vivo and in vitro models, highlight the advantages and drawbacks associated with miRNA-based therapy, and summarize the relevant techniques and approaches attempted to deliver miRNAs to the central nervous system for therapeutic purposes, with particular regard to the exosomes. Additionally, we describe a new approach that holds great promise for the treatment of a wide range of diseases including neurodegenerative disorders. This approach is based on addressing the incorporation of miRNAs into exosomes to increase the quantity and quality of miRNA packed and delivered to the central nervous system and other sites of action.
神经退行性疾病，如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、亨廷顿病和朊病毒病，用常规疗法不能及时有效地治疗。这强调了需要替代治疗方法。在这方面，基于基因的治疗方法已被采用为潜在可行的替代疗法，其中 microRNA（miRNA）方法在近年来经历了巨大的发展。因为已经表明 miRNA 参与了包括神经退行性疾病在内的几种疾病的发病机制，所以它们作为诊断和预后生物标志物的候选物、药物反应的预测因子以及治疗剂进行了深入研究。在这篇综述中，我们评估了直接和间接 miRNA 模拟物和抑制剂在体内和体外模型中调节神经退行性相关基因的可行性，强调了 miRNA 治疗相关的优点和缺点，并总结了为了治疗目的尝试将 miRNA 递送至中枢神经系统而采用的相关技术和方法，特别关注外泌体。此外，我们描述了一种新的方法，该方法为治疗包括神经退行性疾病在内的广泛疾病提供了很大的希望。这种方法基于将 miRNA 纳入外泌体中，以增加被包装并递送至中枢神经系统和其他作用部位的 miRNA 的数量和质量。
