神经轴突生长抑制因子Nogo 家族的研究进展*

Nogo家族是一类神经轴突生长抑制因子家族,目前成员包括Nogo-A,Nogo-B,Nogo-C三个亚型。Nogo家族成员因C末端具有保守的RHD结构域而归属于RTNs家族,表明它们的分布和功能与内质网密切相关。Nogo家族C末端还具有一个进化保守的66氨基酸的功能段称为Nogo-66,体外表达的Nogo-66片段具有抑制神经突生长的作用。Nogo家族成员结构上的区别主要表现在不同剪切长短的N末端序列。Nogo-A主要在中枢和外周神经系统中广泛分布,Nogo-C主要分布在骨骼肌,而Nogo-B则几乎遍布于各种组织与细胞之中。目前,发现可介导Nogo胞内信号转导通路的受体主要是膜外糖蛋白偶联的NgR和跨膜受体p75NTR组成的共受体,但NgR与Nogo-A在胚胎发育中时空表达并不同步提示可能还有其它受体存在。虽然Nogo家族作为神经轴突生长抑制因子被发现,但越来越多的研究表明其可能在胚胎发育、细胞凋亡或神经退行性变等重大事件中扮演重要角色。本文拟就Nogo家族迄今为止突出的研究进展作一综述,旨在为下一步的功能研究工作提供理论参考和依据。

Research Progress of the Neurite Outgrowth Inhibitor Nogo Family*

Nogo family is a kind of neurite outgrowth inhibitor,which includes three family members as far as now.Nogo family belongs to the RTNs family because of the common RHD domains in their C-terminal sequence,which indicates their location and function are related to regulation in cell.Nogo family members also have an conservative 66 amino-acids functional peptide(Nogo-66) in evolutionary process,which has been demonstrated effective in inhibiting neurite outgrowth in vitro.The main difference in family members exists in their different length of N-terminal sequence.Nogo-A has been found sufficient in the CNS or PNS.Nogo-C has been found only in skeloton-musle tissue.While Nogo-B is found almost everywhere in vivo.Presently,the recognized receptors of Nogo are co-receptors including GPI-anchored glycoprotein receptor(NgR)and trans-membrane receptor p75NTR,through which can onset the signaling transduction of ligand in cell.But the obvious different location of Nogo-A and NgR neither in spatial nor in time series when fetus develope,so that other receptors have not been found maybe exist.Although Nogo family is found to be a group of neurite outgrowth inhibitors,more and more researches show their essential roles in important affairs in vivo such as fetus development,cell apoptosis and nerve degradation etc.In this article,we try to review the most outstanding progresses of the Nogo family researches up to now,in order to offer the reference of background information to the future.