John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge , Forvie Site, Robinson Way, Cambridge, UK.
Laboratory for Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW) , Amsterdam, The Netherlands.
Small GTPases. 2020 Nov;11(6):392-401. doi: 10.1080/21541248.2018.1457914. Epub 2018 May 17.
Adult central nervous system (CNS) axons do not regenerate after injury because of extrinsic inhibitory factors, and a low intrinsic capacity for axon growth. Developing CNS neurons have a better regenerative ability, but lose this with maturity. This mini-review summarises recent findings which suggest one reason for regenerative failure is the selective distribution of growth machinery away from axons as CNS neurons mature. These studies demonstrate roles for the small GTPases ARF6 and Rab11 as intrinsic regulators of polarised transport and axon regeneration. ARF6 activation prevents the axonal transport of integrins in Rab11 endosomes in mature CNS axons. Decreasing ARF6 activation permits axonal transport, and increases regenerative ability. The findings suggest new targets for promoting axon regeneration after CNS injury.
成人中枢神经系统 (CNS) 轴突在受伤后不会再生，这是由于外在抑制因子和内在轴突生长能力低所致。发育中的 CNS 神经元具有更好的再生能力，但随着成熟而丧失这种能力。这篇综述总结了最近的发现，这些发现表明再生失败的一个原因是生长机制在 CNS 神经元成熟过程中从轴突的选择性分布。这些研究表明，小 GTPases ARF6 和 Rab11 作为内在调节因子，在极化运输和轴突再生中发挥作用。ARF6 的激活可防止 Rab11 内体中整合素在成熟的 CNS 轴突中的轴突运输。降低 ARF6 的激活可促进轴突运输，并增加再生能力。这些发现为促进 CNS 损伤后的轴突再生提供了新的靶点。
