[Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis]

doi:10.3785/j.issn.1008-9292.2020.08.12

Review

. 2020 Aug 25;49(4):524-530.

doi: 10.3785/j.issn.1008-9292.2020.08.12.

[Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis]

[Article in Chinese]

Shuangshuang Zheng¹, Jingwei Zhao^{1

2

3}

Affiliations

¹ Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou 310058, China.
² Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
³ Cryo-EM Center of Zhejiang University, Hangzhou 310058, China.

PMID: 32985167
PMCID: PMC8800757
DOI: 10.3785/j.issn.1008-9292.2020.08.12

Review

[Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis]

[Article in Chinese]

Shuangshuang Zheng et al. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020.

. 2020 Aug 25;49(4):524-530.

doi: 10.3785/j.issn.1008-9292.2020.08.12.

Authors

Shuangshuang Zheng¹, Jingwei Zhao^{1

2

3}

Affiliations

¹ Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou 310058, China.
² Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
³ Cryo-EM Center of Zhejiang University, Hangzhou 310058, China.

PMID: 32985167
PMCID: PMC8800757
DOI: 10.3785/j.issn.1008-9292.2020.08.12

Abstract
in English, Chinese

Failure to remyelinate and rewrap the demyelinated axons has been revealed as the major hurdle for treatment of multiple sclerosis (MS), and the bottleneck is the inability of oligodendrocyte progenitor cell (OPC) to differentiate into mature oligodendrocyte. Remyelination is a spontaneous regenerative process, which includes activation, migration and differentiation of OPC, and is believed to protect the axon and further halt neurodegeneration. In recent years, studies have identified many potential drug targets for efficiently promoting OPC differentiation in in vivo demyelination models, such as metformin, clemostine, and drug targets as myelin transcription factor 1-like protein (Myt1L), N-methyl-D-aspartic acid (NMDA) receptor, connexin 43 (Cx43), G protein coupled receptor 17 (GPR17), κ opioid receptor (KOR), sterol 14α-demethylase (CYP51), Δ14-sterol reductase (TM7SF2), emopamil-binding protein (EBP). This review summarizes the recent progress on the mechanisms underlying the activation, migration and differentiation of OPC in remyelination with special focus on studies using demyelination models of MS, which may provide insights of further exploring new therapeutic strategies for MS.

在多发性硬化症患者的中枢神经系统中，脱髓鞘的轴突难以有效复髓鞘是治疗疾病的主要障碍，而髓鞘再生失败的瓶颈问题是少突胶质细胞前体细胞（OPC）不能分化为成熟的少突胶质细胞。复髓鞘是继脱髓鞘后自然发生的再生反应，包括OPC的激活、迁移和分化；具有保护神经轴突、进而避免神经元变性坏死的作用。近年来在体脱髓鞘模型研究发现，二甲双胍、氯马斯汀能有效加强复髓鞘，鉴定了髓鞘转录因子1样蛋白（Myt1L）、 N-甲基- D-天门冬氨酸（NMDA）受体、星形细胞连接蛋白43（Cx43）、G蛋白偶联受体17（GPR17）、κ阿片受体（KOR）、甾醇14α-脱甲基化酶（CYP51）、脱氢胆固醇还原酶14（TM7SF2）和3-β-羟基类固醇-8，7-异构酶（EBP）等促进OPC分化的潜在药物靶点。本文基于对复髓鞘机制的理解，讨论了促进OPC分化和增强复髓鞘的研究进展，这些进展为进一步研发治疗多发性硬化症的新方法提供了思路。

Keywords: Multiple sclerosis; Oligodendrocyte progenitor cells; Remyelination.

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References

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1. FRANKLIN R, FFRENCH-CONSTANT C. Regenerating CNS myelin-from mechanisms to experimental medicines. Nat Rev Neurosci. 2017;18(12):753–769. doi: 10.1038/nrn.2017.136. [FRANKLIN R, FFRENCH-CONSTANT C. Regenerating CNS myelin-from mechanisms to experimental medicines[J]. Nat Rev Neurosci, 2017, 18(12):753-769. DOI:10.1038/nrn.2017.136. ] - DOI - PubMed
1. FVNFSCHILLING U, SUPPLIE L M, MAHAD D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485(7399):517–521. doi: 10.1038/nature11007. [FVNFSCHILLING U, SUPPLIE L M, MAHAD D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity[J]. Nature, 2012, 485(7399):517-521. DOI:10.1038/nature11007. ] - DOI - PMC - PubMed

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国家重点研发计划（2017YFA0104900）；国家自然科学基金（81971144，81571170）；后勤保障部重点项目（BZZ19J005）；宁夏回族自治区重点研发计划（2019BFH02012）

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[1] NAVE K A, WERNER H B. Myelination of the nervous system:mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503–533. doi: 10.1146/annurev-cellbio-100913-013101. [NAVE K A, WERNER H B. Myelination of the nervous system:mechanisms and functions[J]. Annu Rev Cell Dev Biol, 2014, 30:503-533. DOI:10.1146/annurev-cellbio-100913-013101. ] - DOI - PubMed

[2] NAVE K A, WERNER H B. Myelination of the nervous system:mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503–533. doi: 10.1146/annurev-cellbio-100913-013101. [NAVE K A, WERNER H B. Myelination of the nervous system:mechanisms and functions[J]. Annu Rev Cell Dev Biol, 2014, 30:503-533. DOI:10.1146/annurev-cellbio-100913-013101. ] - DOI - PubMed

[3] NAVE K A. Myelination and the trophic support of long axons. Nat Rev Neurosci. 2010;11(4):275–283. doi: 10.1038/nrn2797. [NAVE K A. Myelination and the trophic support of long axons[J]. Nat Rev Neurosci, 2010, 11(4):275-283. DOI:10.1038/nrn2797. ] - DOI - PubMed

[4] NAVE K A. Myelination and the trophic support of long axons. Nat Rev Neurosci. 2010;11(4):275–283. doi: 10.1038/nrn2797. [NAVE K A. Myelination and the trophic support of long axons[J]. Nat Rev Neurosci, 2010, 11(4):275-283. DOI:10.1038/nrn2797. ] - DOI - PubMed

[5] DUNCAN I D, BROWER A, KONDO Y, et al. Extensive remyelination of the CNS leads to functional recovery. Proc Natl Acad Sci U S A. 2009;106(16):6832–6836. doi: 10.1073/pnas.0812500106. [DUNCAN I D, BROWER A, KONDO Y, et al. Extensive remyelination of the CNS leads to functional recovery[J]. Proc Natl Acad Sci U S A, 2009, 106(16):6832-6836. DOI:10.1073/pnas.0812500106. ] - DOI - PMC - PubMed

[6] DUNCAN I D, BROWER A, KONDO Y, et al. Extensive remyelination of the CNS leads to functional recovery. Proc Natl Acad Sci U S A. 2009;106(16):6832–6836. doi: 10.1073/pnas.0812500106. [DUNCAN I D, BROWER A, KONDO Y, et al. Extensive remyelination of the CNS leads to functional recovery[J]. Proc Natl Acad Sci U S A, 2009, 106(16):6832-6836. DOI:10.1073/pnas.0812500106. ] - DOI - PMC - PubMed

[7] FRANKLIN R, FFRENCH-CONSTANT C. Regenerating CNS myelin-from mechanisms to experimental medicines. Nat Rev Neurosci. 2017;18(12):753–769. doi: 10.1038/nrn.2017.136. [FRANKLIN R, FFRENCH-CONSTANT C. Regenerating CNS myelin-from mechanisms to experimental medicines[J]. Nat Rev Neurosci, 2017, 18(12):753-769. DOI:10.1038/nrn.2017.136. ] - DOI - PubMed

[8] FRANKLIN R, FFRENCH-CONSTANT C. Regenerating CNS myelin-from mechanisms to experimental medicines. Nat Rev Neurosci. 2017;18(12):753–769. doi: 10.1038/nrn.2017.136. [FRANKLIN R, FFRENCH-CONSTANT C. Regenerating CNS myelin-from mechanisms to experimental medicines[J]. Nat Rev Neurosci, 2017, 18(12):753-769. DOI:10.1038/nrn.2017.136. ] - DOI - PubMed

[9] FVNFSCHILLING U, SUPPLIE L M, MAHAD D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485(7399):517–521. doi: 10.1038/nature11007. [FVNFSCHILLING U, SUPPLIE L M, MAHAD D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity[J]. Nature, 2012, 485(7399):517-521. DOI:10.1038/nature11007. ] - DOI - PMC - PubMed

[10] FVNFSCHILLING U, SUPPLIE L M, MAHAD D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485(7399):517–521. doi: 10.1038/nature11007. [FVNFSCHILLING U, SUPPLIE L M, MAHAD D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity[J]. Nature, 2012, 485(7399):517-521. DOI:10.1038/nature11007. ] - DOI - PMC - PubMed

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[Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis]

Affiliations

[Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis]

Authors

Affiliations

Abstract
in English, Chinese

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Abstract in English, Chinese

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Abstract
in English, Chinese