Molecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, UK.
Brain Res Bull. 2011 Mar 10;84(4-5):289-99. doi: 10.1016/j.brainresbull.2010.08.004. Epub 2010 Aug 13.
The reasons for the failure of central nervous system (CNS) axons to regenerate include the presence of myelin- and non-myelin derived inhibitory molecules, neuronal apoptosis and the absence of a potent neurotrophic stimulus. Transactivation of the epidermal growth factor receptor (EGFR) has been implicated in signalling inhibition of axon growth in the CNS. Small molecule EGFR inhibitors such as AG1478 and PD168393 promote CNS axon growth after optic nerve transection despite the presence of inhibitory molecules in the environment of the regenerating axon. However, our results demonstrate that phosphorylated EGFR (pEGFR) is not present on regenerating axons and that the majority of pEGFR is present in glia, suggesting that EGFR cannot play a direct intra-axonal role in signalling inhibition and thus disinhibited CNS axon growth must be indirectly mediated by glia. We argue that EGFR may not have a role in signalling axon growth inhibition since AG1478 and PD168393 promotes neuronal neurite outgrowth in CNS myelin-inhibited cultures after EGFR knockdown. This review discusses the current evidences for and against the involvement of EGFR in signalling myelin inhibition.
中枢神经系统（CNS）轴突再生失败的原因包括髓鞘和非髓鞘来源的抑制分子、神经元凋亡以及缺乏有效的神经营养刺激。表皮生长因子受体（EGFR）的转激活已被牵连到 CNS 轴突生长信号抑制中。尽管再生轴突的环境中存在抑制分子，但小分子 EGFR 抑制剂如 AG1478 和 PD168393 可促进视神经切断后的 CNS 轴突生长。然而，我们的结果表明，再生轴突上不存在磷酸化的 EGFR（pEGFR），而大部分 pEGFR 存在于神经胶质细胞中，这表明 EGFR 不能在信号传导抑制中发挥直接的轴内作用，因此去抑制的 CNS 轴突生长必须由神经胶质细胞间接介导。我们认为 EGFR 可能没有在信号传导轴突生长抑制中发挥作用，因为在 EGFR 敲低后，AG1478 和 PD168393 可促进 CNS 髓鞘抑制培养中的神经元神经突生长。这篇综述讨论了 EGFR 参与信号转导髓鞘抑制的现有证据。
