Laboratory for Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Strasse 27, 53127 Bonn, Germany.
Curr Opin Neurobiol. 2018 Aug;51:60-69. doi: 10.1016/j.conb.2018.02.024. Epub 2018 Mar 12.
Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone. The cytoskeleton also drives the migration of scar-forming cells after an injury. Targeting its dynamics modifies the composition of the inhibitory environment formed by scar tissue and renders it more permissive for regenerating axons. Hence, cytoskeleton dynamics represent an appealing target to promote axon regeneration. As some of cytoskeleton-targeting drugs are used in the clinics for other purposes, they hold the promise to be used as a basis for a regenerative therapy after a spinal cord injury.
近年来，细胞骨架动态已成为轴突再生的关键因素。细胞骨架，特别是微管和肌动蛋白，确保神经元过程的生长，并维持神经元的独特、高度极化的形状。损伤后，成年中枢轴突被退行性结构——回缩球所阻断，阻止其再生。异常的细胞骨架动力学导致了这种生长无能结构的形成，但通过药理学调节损伤轴突的细胞骨架动力学，可以将这种结构转化为具有生长能力的生长锥。细胞骨架还驱动损伤后瘢痕形成细胞的迁移。靶向其动力学可以改变由瘢痕组织形成的抑制性环境的组成，使其对再生轴突更具渗透性。因此，细胞骨架动力学是促进轴突再生的一个有吸引力的目标。由于一些针对细胞骨架的药物已经在临床上用于其他用途，因此它们有望成为脊髓损伤后再生治疗的基础。
