少突胶质细胞的功能与脱髓鞘疾病

Function of oligodendrocytes and demyelinating disease

背景:脱髓鞘疾病是以神经髓鞘脱失为主、神经元胞体及轴突相对损伤较轻为特征的一种疾病。正常生理条件下,髓鞘脱失后机体会自发地进行髓鞘再生,但在病理条件下,该过程会因多种因素被抑制,导致髓鞘再生不完全或失败,使脱髓鞘发展,病情持续加重。目的:文章强调了少突胶质细胞在髓鞘再生过程中的重要性,以及如何从少突胶质细胞的角度开展以药物和细胞为基础的脱髓鞘疾病药物的研发,以期为脱髓鞘疾病的药物开发提供新的途径。方法:利用PubMed、GeenMedical和中国知网等数据库检索、筛选与少突胶质细胞和脱髓鞘疾病相关或涉及少突胶质前体细胞、少突胶质细胞相关功能以及髓鞘再生方面的文献,英文检索词为"oligodendrocyte,demyelinating disease",中文检索词为"少突胶质细胞、脱髓鞘疾病",检索时间从各数据库建库至2021-05-01,共纳入参考文献142篇。结果与结论:(1)少突胶质细胞在脱髓鞘疾病中对于髓鞘再生的作用至关重要,炎性微环境中,少突胶质细胞的功能会受到损伤并损害轴突传导,维持少突胶质细胞在中枢神经系统中的功能对于脱髓鞘疾病的治疗至关重要。(2)目前,针对脱髓鞘疾病新的治疗策略层出不穷,主要以预防炎症为主。如通过生物信息技术手段筛选出可用的小分子化合物或经美国食品和药物管理局批准的药物为筛选对象开发出可以靶向调节髓鞘再生不同阶段内在或外在信号的药物,以及移植具有分化为少突胶质细胞能力的中枢神经系统干细胞至病灶区域的细胞疗法。现行研究的治疗切入点各有千秋,研发出低成本、低不良反应、高药物疗效、高效益的治疗策略还将面临艰巨的挑战。

BACKGROUND:Demyelination diseases are a disease that presents loss of myelin,and relative light damage to neuronal cell body and axon.Under normal physiological conditions,the body will spontaneously carry out remyelination after demyelination.However,under pathological conditions,this process can be inhibited by many factors,resulting in incompletion or failure of myelin sheath regeneration,making demyelination development,and the diseases can continue to aggravate.OBJECTIVE:To emphasize the critical role of oligodendrocytes in the process of remyelination,how to develop drugs and cell-based demyelinating disease drugs from the perspective of oligodendrocytes so as to provide a new approach for drug development of demyelinating diseases.METHODS:Databases of PubMed,GeenMedical,and CNKI were searched for the articles regarding oligodendrocytes and demyelinating diseases or involving oligodendrocyte precursor cells,oligodendrocyte-related functions,and remyelination published from the inception to May 1,2021.The key words were"oligodendrocyte,demyelinating diseases"in English and Chinese.Totally 142 articles were included.RESULTS AND CONCLUSION:(1)The role of oligodendrocytes in demyelinating diseases is essential for remyelination.In inflammatory microenvironments,the function of oligodendrocytes can be impaired and damage axonal conduction.Therefore,maintaining the function of oligodendrocytes in the central nervous system is crucial to treat demyelinating diseases.(2)At present,new treatment strategies for demyelinating diseases are endless,mainly to prevent inflammation.For example,bioinformatics technology is used to screen available small molecule compounds.Alternatively,some drugs approved by Food and Drug Administration are developed to screen subjects.Or drugs have been developed that target internal and external signals at different stages of myelin regeneration.Furthermore,there are also cell therapies for transplantation of central nervous system stem cells with the ability to differentiate into oligodendrocytes to the affected area.The current research has its various treatment entry points,and the development of low-cost,low side effects,high drug efficacy,and high-efficiency treatment strategies also face arduous challenges.