少突胶质细胞分化抑制因子及其在多发性硬化症中的作用

Oligodendrocyte differentiation inhibiting factors and their regulation in multiple sclerosis

多发性硬化症(multiple sclerosis,MS)是一种慢性炎症性脱髓鞘疾病,中枢神经系统的主要表现为脱髓鞘及疾病晚期修复失代偿。少突胶质细胞(oligodendrocytes,OLs)的成熟障碍是MS慢性脱髓鞘病灶髓鞘再生失败的主要原因。OLs成熟的整个过程受到细胞内在和外在因素复杂而精确的调控,Notch1、Wnt/β-连环蛋白、LINGO1、骨成形蛋白4和透明质酸/Toll样受体2等信号通路及Hes5、ID2、ID4、Y染色体性别决定区相关高迁移率族蛋白盒5和Y染色体性别决定区相关高迁移率族蛋白盒6等转录因子家族均参与抑制OLs的分化和髓鞘形成。受损神经纤维周围的炎症环境在MS病灶髓鞘再生中也起重要调节作用。近年来,大量OLs分化抑制因子的发现,为髓鞘再生治疗提供了新的分子靶点。作者就OLs分化抑制因子及其在MS中作用的研究进展作一综述。

Multiple sclerosis( MS) is a chronic inflammatory demyelinating disease characterized by demyelination and poor repair of lesions at the advanced stage in central nervous system( CNS). Till now,oligodendrocyte maturation defects are seen as major causes of poor remyelination in MS. The mechanisms involved in the accurate regulation of oligodendrocytes( OLs) maturation include the intrinsic and extrinsic cues,as well as intricate interactions between them. Both signaling including Notch1,Wnt / β-catenin,LINGO1,BMP4,HA / TLR2 and transcriptional factors including Hes5,ID2,ID4,sex determination region of Y chromosome-related high mobility group box( Sox)5 and Sox6 have been identified as an important repressive regulator of the differentiation of OLs and myelination. The local inflammatory milieu also appears to play critical and conflicting roles in promotion and inhibition of remyelination in MS. Many new inhibiting factors towards OLs differentiation represent an exciting and important initial step towards developing new molecular therapeutics targeting disability in MS. Here,we provide an overview of these inhibiting factors and their regulation in MS.