Disruption of Sema3A/Plexin-A1 inhibitory signalling in oligodendrocytes as a therapeutic strategy to promote remyelination

被引：30

作者：

Biname, Fabien ^{[1
]}

Pham-Van, Lucas D. ^{[1
]}

Spenle, Caroline ^{[1
]}

Jolivel, Valerie ^{[1
]}

Birmpili, Dafni ^{[1
]}

Meyer, Lionel A. ^{[1
]}

Jacob, Laurent ^{[1
]}

Meyer, Laurence ^{[1
]}

Mensah-Nyagan, Ayikoe G. ^{[1
]}

Po, Chrystelle ^{[2
]}

Van der Heyden, Michael ^{[1
]}

Roussel, Guy ^{[1
]}

Bagnard, Dominique ^{[1
]}

机构：

[1] Strasbourg Univ, Federat Med Translat Strasbourg, Labex Medalis, INSERM U1119 Biopathol Myelin,Neuroprotect,Therap, Strasbourg, France

[2] Strasbourg Univ, Fac Med, Inst Phys Biol, Strasbourg, France

来源：

EMBO MOLECULAR MEDICINE | 2019年 / 11卷 / 11期

关键词：

multiple sclerosis; myelination; oligodendrocyte; Plexin; Semaphorin; TRANSMEMBRANE DOMAIN; PRECURSOR CELLS; DEMYELINATION; MEDIATOR; SEMAPHORINS; EXPRESSION; RECEPTORS; MIGRATION; GUIDANCE; PLEXINS;

D O I：

10.15252/emmm.201910378

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Current treatments in multiple sclerosis (MS) are modulating the inflammatory component of the disease, but no drugs are currently available to repair lesions. Our study identifies in MS patients the overexpression of Plexin-A1, the signalling receptor of the oligodendrocyte inhibitor Semaphorin 3A. Using a novel type of peptidic antagonist, we showed the possibility to counteract the Sema3A inhibitory effect on oligodendrocyte migration and differentiation in vitro when antagonizing Plexin-A1. The use of this compound in vivo demonstrated a myelin protective effect as shown with DTI-MRI and confirmed at the histological level in the mouse cuprizone model of induced demyelination/remyelination. This effect correlated with locomotor performances fully preserved in chronically treated animals. The administration of the peptide also showed protective effects, leading to a reduced severity of demyelination in the context of experimental autoimmune encephalitis (EAE). Hence, the disruption of the inhibitory microenvironmental molecular barriers allows normal myelinating cells to exert their spontaneous remyelinating capacity. This opens unprecedented therapeutic opportunity for patients suffering a disease for which no curative options are yet available.

引用

页数：16

共 29 条

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