Fawcett J W
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambrige, UK.
Eye (Lond). 2017 Feb;31(2):206-208. doi: 10.1038/eye.2016.293. Epub 2016 Dec 23.
Axon regeneration in the CNS is blocked by inhibitory molecules in the environment and by a developmental loss of regenerative potential in CNS axons. Axon growth is a specialized form of cell migration, and for any cell to migrate there must be an adhesion molecule at the growth tip that recognizes a ligand in the environment, and which is linked to signaling and cytoskeletal mechanisms. The reasons for this loss of regenerative ability in CNS axons are several, but important contributors are the developmental loss of integrins that recognize ligands in the mature CNS environment, and selective trafficking of integrins and other molecules to exclude them from axons and direct them to dendrites. Regeneration of sensory axons in the spinal cord can be achieved by expression of tenascin-binding α9-integrin together with the integrin activator kindlin-1. This works because integrins are transported into sensory axons. Transport of integrins into retinal ganglion cell axons is seen in the retina, but may become more restricted in the optic nerve, with a subset of axons containing expressed integrins. Transduction of ganglion cells with α9-integrin and kindlin-1 should promote regeneration of this subset of axons, but attention to transport may be required for regeneration of the remaining axons.
中枢神经系统（CNS）中的轴突再生受到环境中抑制性分子以及CNS轴突再生潜能的发育性丧失的阻碍。轴突生长是细胞迁移的一种特殊形式，对于任何细胞的迁移而言，生长尖端必须存在一种黏附分子，该分子能够识别环境中的配体，并与信号传导和细胞骨架机制相联系。CNS轴突再生能力丧失的原因有多种，但重要因素包括在成熟CNS环境中识别配体的整合素的发育性丧失，以及整合素和其他分子的选择性运输，从而将它们排除在轴突之外并引导至树突。通过表达与整合素激活剂kindlin-1共同结合腱生蛋白的α9-整合素，可实现脊髓中感觉轴突的再生。这之所以有效，是因为整合素被转运到感觉轴突中。在视网膜中可观察到整合素向视网膜神经节细胞轴突的转运，但在视神经中可能会受到更多限制，只有一部分轴突含有表达的整合素。用α9-整合素和kindlin-1转导神经节细胞应能促进这部分轴突的再生，但对于其余轴突的再生可能需要关注其转运情况。
