Intracellular signaling pathway regulation of myelination and remyelination in the CNS.
Intracellular signaling pathway regulation of myelination and remyelination in the CNS.
复制标题
DOI：
10.1016/j.expneurol.2016.03.008
复制
发表时间：
2016-09
影响因子：
5.3
通讯作者：
Fyffe-Maricich, Sharyl L.
中科院分区：
文献类型：
--
作者：
Gaesser, Jenna M.;Fyffe-Maricich, Sharyl L.
关键词：
脱髓鞘轴突上髓鞘的修复仍然是多发性硬化症(MS)治疗的主要障碍。目前批准的治疗方法是通过调节免疫系统来减少病变形成的数量和速度，但由于无法恢复丢失的髓鞘，因此只有部分有效。在健康的中枢神经系统中，髓鞘在一生中持续产生，自发的髓鞘再生很容易对侮辱做出反应。然而，在MS患者中，重新髓鞘形成最终失败，至少部分原因是少突胶质前体细胞(OPC)分化失败，随后产生新的髓鞘。因此，更好地了解驱动髓鞘形成过程的分子机制和信号通路对于加快针对髓鞘再分化的新疗法的开发是重要的。在这里，我们回顾了三个高度保守的细胞内信号通路：WnT/β-连环蛋白、PI3K/AKT/mTOR和ERK/MAPK在OPC分化和髓鞘形成过程中的调节作用。文中还讨论了这三条通路之间的潜在串扰点和未来研究的重要领域。
The restoration of myelin sheaths on demyelinated axons remains a major obstacle in the treatment of multiple sclerosis (MS). Currently approved therapies work by modulating the immune system to reduce the number and rate of lesion formation but are only partially effective since they are not able to restore lost myelin. In the healthy CNS, myelin continues to be generated throughout life and spontaneous remyelination occurs readily in response to insults. In patients with MS, however, remyelination eventually fails, at least in part as a result of a failure of oligodendrocyte precursor cell (OPC) differentiation and the subsequent production of new myelin. A better understanding of the molecular mechanisms and signaling pathways that drive the process of myelin sheath formation is therefore important in order to speed the development of novel therapeutics designed to target remyelination. Here we review data supporting critical roles for three highly conserved intracellular signaling pathways: Wnt/β-catenin, PI3K/AKT/mTOR, and ERK/MAPK in the regulation of OPC differentiation and myelination both during development and in remyelination. Potential points of crosstalk between the three pathways and important areas for future research are also discussed.
登录
查看更多内容
影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
4.2
作者：
Bansal, R;Magge, S;Winkler, S
通讯作者：
Winkler, S
影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
Wnt/β-连环蛋白信号传导对少突胶质细胞发育的阶段特异性调节
影响因子：
5.3
作者：
Dai, Zhong-Min;Sun, Shuhui;Qiu, Mengsheng
通讯作者：
Qiu, Mengsheng
影响因子：
3.5
作者：
Baron, W;Metz, B;de Vries, H
通讯作者：
de Vries, H