Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China.
Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5930, USA.
Prog Neurobiol. 2019 Dec;183:101694. doi: 10.1016/j.pneurobio.2019.101694. Epub 2019 Sep 19.
Exosomes are small bilipid layer-enclosed extracellular vesicles that can be found in tissues and biological fluids. As a key cell-to-cell and distant communication mediator, exosomes are involved in various central nervous system (CNS) diseases, potentially through transferring their contents such as proteins, lipids and nucleic acids to the target cells. Exosomal miRNAs, which are small non-coding RNAs in the exosomes, are known to be more stable than free miRNAs and therefore have lasting effects on disease-related gene expressions. There are distinct profiles of exosomal miRNAs in different types of CNS diseases even before the onset of irreversible neurological damages, indicating that exosomal miRNAs within tissues and biological fluids could serve as promising biomarkers. Emerging evidence has also demonstrated the pathological effects of several exosomal miRNAs in CNS diseases via specific modulation of disease-related factors. Moreover, exosomes carry therapeutically beneficial miRNAs across the blood-brain-barrier, which can be exploited as a powerful drug delivery tool to help alleviating multiple CNS diseases. In this review, we summarize the recent progress made in understanding the biological roles of exosomal miRNAs as potential diagnostic biomarkers, pathological regulators, and therapeutic targets/drugs for CNS diseases. A comprehensive discussion of the main concerns and challenges for the applications of exosomal miRNAs in the clinical setting is also provided.
外泌体是一种双层脂包裹的小型细胞外囊泡，可在组织和生物液中发现。作为一种关键的细胞间和远距离通讯介质，外泌体参与了各种中枢神经系统 (CNS) 疾病，可能通过将其内容物（如蛋白质、脂质和核酸）转移到靶细胞来发挥作用。外泌体中的微小 RNA (miRNA) 是小的非编码 RNA，已知比游离 miRNA 更稳定，因此对与疾病相关的基因表达具有持久影响。在不可逆的神经损伤发生之前，不同类型的 CNS 疾病中外泌体 miRNA 存在明显的特征性差异，这表明组织和生物液中的外泌体 miRNA 可作为有前途的生物标志物。新出现的证据还表明，几种外泌体 miRNA 通过特定调节与疾病相关的因素，在 CNS 疾病中具有病理性作用。此外，外泌体携带治疗益处的 miRNA 通过血脑屏障，可作为一种强大的药物输送工具，有助于缓解多种 CNS 疾病。在这篇综述中，我们总结了理解外泌体 miRNA 作为潜在诊断生物标志物、病理调节因子和 CNS 疾病治疗靶点/药物的生物学作用的最新进展。还全面讨论了外泌体 miRNA 在临床应用中的主要关注点和挑战。
