Laboratory of Nervous System Injuries and Diseases, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children at Sichuan University, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
Neuroscientist. 2023 Jun;29(3):287-301. doi: 10.1177/10738584221083919. Epub 2022 Apr 3.
Myelination by oligodendrocytes is crucial for neuronal survival and function, and defects in myelination or failure in myelin repair can lead to axonal degeneration and various neurological diseases. At present, the factors that promote myelination and overcome the remyelination block in demyelinating diseases are poorly defined. Although the roles of protein-coding genes in oligodendrocyte differentiation have been extensively studied, the majority of the mammalian genome is transcribed into noncoding RNAs, and the functions of these molecules in myelination are poorly characterized. Long noncoding RNAs (lncRNAs) regulate transcription at multiple levels, providing spatiotemporal control and robustness for cell type-specific gene expression and physiological functions. lncRNAs have been shown to regulate neural cell-type specification, differentiation, and maintenance of cell identity, and dysregulation of lncRNA function has been shown to contribute to neurological diseases. In this review, we discuss recent advances in our understanding of the functions of lncRNAs in oligodendrocyte development and myelination as well their roles in neurological diseases and brain tumorigenesis. A more systematic characterization of lncRNA functional networks will be instrumental for a better understanding of CNS myelination, myelin disorders, and myelin repair.
少突胶质细胞的髓鞘形成对于神经元的存活和功能至关重要，髓鞘形成缺陷或髓鞘修复失败可导致轴突变性和各种神经退行性疾病。目前，促进髓鞘形成和克服脱髓鞘疾病中髓鞘再生障碍的因素还未被明确界定。尽管蛋白编码基因在少突胶质细胞分化中的作用已被广泛研究，但哺乳动物基因组的大部分转录为非编码 RNA，这些分子在髓鞘形成中的功能仍未被充分阐明。长非编码 RNA（lncRNA）在多个水平上调节转录，为细胞类型特异性基因表达和生理功能提供时空控制和稳健性。lncRNA 已被证明可调节神经细胞类型特化、分化和细胞身份的维持，lncRNA 功能失调已被证明与神经退行性疾病有关。在这篇综述中，我们讨论了近期对 lncRNA 在少突胶质细胞发育和髓鞘形成中的功能以及它们在神经退行性疾病和脑肿瘤发生中的作用的理解的进展。更系统地描述 lncRNA 功能网络将有助于更好地理解中枢神经系统髓鞘形成、髓鞘疾病和髓鞘修复。
