神经退行疾病中髓鞘再生及microRNA的调控机制

Remyelination Regulated by microRNAs in Neurodegenerative Diseases: A Review

中枢神经系统脱髓鞘多发于神经退行性疾病中,如多发性硬化症(MS)。髓鞘是包裹在轴突上的一层髓磷脂膜,为神经元起到冲动的快速传导和代谢耦合的作用,若轴突裸漏,则导致轴突变性,进而导致神经元变性,此为脱髓鞘性神经退行性疾病患者机体功能障碍甚至致残的主要原因。其中除了成熟髓鞘脱失,髓鞘再生障碍也是导致疾病发展的重要原因之一。髓鞘由少突胶质细胞(OLs)组成,其由神经干细胞(NSC)分化为少突胶质祖细胞(OPCs),进而分化为成熟的少突胶质细胞。髓鞘再生过程即为从NSCs分化为形成髓鞘的少突胶质细胞的过程,近年来的研究发现此过程受众多基因调控。微小核糖核酸(microRNA)作为神经退行性疾病的重要调节因子,在髓鞘再生环节中形成复杂的调控网络。该文总结了髓鞘再生的主要分子途径及参与此过程的microRNA,并对其作用机制及其靶点进行归纳和分类,并总结了目前中医药促进髓鞘再生的治疗方法和通过microRNA发挥神经保护功能的药物。该综述有望对未来针对调控microRNA治疗脱髓鞘疾病的研究提供理论参考和研究指引。

Demyelination of the central nervous system often occurs in neurodegenerative diseases,such as multiple sclerosis(MS).The myelin sheath,a layer of myelin membrane wrapping the axon,plays a role in the rapid conduction and metabolic coupling of impulses for neurons.The exposure of the axon will lead to axonal degeneratio,and further neuronal degeneration,which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases.In addition to the demyelination of mature myelin sheath,remyelination disorder is also one of the major reasons leading to the development of the diseases.The myelin sheath is composed of oligodendrocytes(OLs)derived from oligodendrocyte progenitor cells(OPCs)which are differentiated from neural stem cells(NSCs).The process of myelin regeneration,i.e.,remyelination,is the differentiation of NSCs into OLs.Recent studies have shown that this process is regulated by a variety of genes.MicroRNAs,as important regulators of neurodegenerative diseases,form a complex regulatory network in the process of myelin regeneration.This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets.This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.