表皮生长因子受体（EGFR）激活介导髓磷脂和硫酸软骨素蛋白聚糖对轴突再生的抑制作用。

EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans.

作者信息

Koprivica Vuk, Cho Kin-Sang, Park Jong Bae, Yiu Glenn, Atwal Jasvinder, Gore Bryan, Kim Jieun A, Lin Estelle, Tessier-Lavigne Marc, Chen Dong Feng, He Zhigang

机构信息

Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.

出版信息

Science. 2005 Oct 7;310(5745):106-10. doi: 10.1126/science.1115462.

DOI:10.1126/science.1115462

PMID:16210539

Abstract

Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

摘要

与髓磷脂和胶质瘢痕相关的抑制性分子限制了成体中枢神经系统（CNS）中的轴突再生，但其再生抑制的潜在信号传导机制尚未完全明确。在此，我们表明抑制表皮生长因子受体（EGFR）的激酶功能可阻断髓磷脂抑制剂和硫酸软骨素蛋白聚糖在抑制神经突生长方面的活性。此外，再生抑制剂以钙依赖的方式触发EGFR的磷酸化。局部施用EGFR抑制剂可促进受损视神经纤维的显著再生，为增强中枢神经系统损伤后的轴突再生指明了一条有前景的治疗途径。