Department of Neurosurgery, University of New Mexico Health Sciences Center, 1101 Yale Blvd, Albuquerque, NM, 87106-3834, USA.
Neurochem Res. 2020 Jan;45(1):188-203. doi: 10.1007/s11064-019-02777-6. Epub 2019 Mar 15.
microRNAs (miRNAs) are recently identified small RNA molecules that regulate gene expression and significantly influence the essential cellular processes associated with CNS repair after trauma and neuropathological conditions including stroke and neurodegenerative disorders. A number of specific miRNAs are implicated in regulating the development and propagation of CNS injury, as well as its subsequent regeneration. The review focuses on the functions of the miRNAs and their role in brain recovery following CNS damage. The article introduces a brief description of miRNA biogenesis and mechanisms of miRNA-induced gene suppression, followed by an overview of miRNAs involved in the processes associated with CNS repair, including neuroprotection, neuronal plasticity and axonal regeneration, vascular reorganization, neuroinflammation, and endogenous stem cell activation. Specific emphasis is placed on the role of multifunctional miRNA miR-155, as it appears to be involved in multiple neurorestorative processes during different CNS pathologies. In association with our own studies on miR-155, I introduce a new and unexplored approach to cerebral regeneration: regulation of brain tissue repair through a direct modulation of specific miRNA activity. The review concludes with discussion on the challenges and the future potential of miRNA-based therapeutic approaches to CNS repair.
微小 RNA(miRNAs)是最近发现的小 RNA 分子,可调节基因表达,并显著影响创伤后中枢神经系统修复以及包括中风和神经退行性疾病在内的神经病理状况相关的基本细胞过程。许多特定的 miRNAs 参与调节中枢神经系统损伤的发展和传播,以及其随后的再生。本综述重点介绍了 miRNAs 的功能及其在中枢神经系统损伤后的脑恢复中的作用。文章介绍了 miRNA 生物发生的简要描述和 miRNA 诱导基因抑制的机制,接着概述了与中枢神经系统修复相关的过程中涉及的 miRNAs,包括神经保护、神经元可塑性和轴突再生、血管重建、神经炎症和内源性干细胞激活。特别强调多功能 miRNA miR-155 的作用,因为它似乎参与了不同中枢神经系统疾病中的多种神经修复过程。结合我们自己关于 miR-155 的研究,我提出了一种新的、尚未探索的大脑再生方法:通过直接调节特定 miRNA 活性来调节脑组织修复。该综述最后讨论了 miRNA 为基础的中枢神经系统修复治疗方法的挑战和未来潜力。