Department of Biological Sciences, University of South Carolina, Columbia, SC 20208, USA.
Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Exp Neurol. 2014 Apr;254:12-7. doi: 10.1016/j.expneurol.2013.12.025. Epub 2014 Jan 11.
The remarkably poor regeneration of axons seen after injury of the brain and spinal cord can result in permanent loss of neural function. This failure of meaningful regeneration has been attributed to both a low intrinsic growth potential of CNS neurons and extrinsic factors that actively block axon growth in the adult CNS. Injury exacerbates this situation by increasing the expression of and exposure to proteins that actively block axonal growth in the CNS. Much experimental efforts have been aimed at overcoming the extrinsic growth inhibitory environment of the injured brain and spinal cord. A recent publication in Experimental Neurology from Kuboyama and colleagues shows that activation of protein kinase A signaling is responsible for the stalling of axon growth in gradients of CNS inhibitory molecules. This observation is unexpected given the role of cAMP signaling in supporting intrinsic growth mechanisms, emphasizing the need to consider spatial and temporal aspects of intracellular signaling in future strategies for neural repair.
大脑和脊髓损伤后轴突的再生能力极差，可导致神经功能的永久性丧失。这种有意义的再生失败归因于中枢神经系统神经元的内在生长潜力低和外在因素，这些因素在成人中枢神经系统中积极阻止轴突生长。损伤通过增加主动阻断中枢神经系统轴突生长的蛋白质的表达和暴露来加剧这种情况。大量实验努力旨在克服受伤大脑和脊髓的外在生长抑制环境。最近发表在《实验神经病学》上的一篇 Kuboyama 及其同事的论文表明，蛋白激酶 A 信号的激活负责中枢神经系统抑制性分子梯度中轴突生长的停滞。鉴于 cAMP 信号在支持内在生长机制中的作用，这一观察结果出乎意料，强调在未来的神经修复策略中需要考虑细胞内信号的空间和时间方面。
