Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA.
Cells. 2021 May 26;10(6):1325. doi: 10.3390/cells10061325.
Axon regeneration after injury is a conserved biological process that involves a large number of molecular pathways, including rapid calcium influx at injury sites, retrograde injury signaling, epigenetic transition, transcriptional reprogramming, polarized transport, and cytoskeleton reorganization. Despite the numerous efforts devoted to understanding the underlying cellular and molecular mechanisms of axon regeneration, the search continues for effective target molecules for improving axon regeneration. Although there have been significant historical efforts towards characterizing pro-regenerative factors involved in axon regeneration, the pursuit of intrinsic inhibitors is relatively recent. EFA6 (exchange factor for ARF6) has been demonstrated to inhibit axon regeneration in different organisms. EFA6 inhibition could be a promising therapeutic strategy to promote axon regeneration and functional recovery after axon injury. This review summarizes the inhibitory role on axon regeneration through regulating microtubule dynamics and through affecting ARF6 (ADP-ribosylation factor 6) GTPase-mediated integrin transport.
轴突损伤后的再生是一种保守的生物学过程，涉及许多分子途径，包括损伤部位的快速钙内流、逆行损伤信号、表观遗传转换、转录重编程、极化运输和细胞骨架重组。尽管人们为了解析轴突再生的潜在细胞和分子机制做出了大量努力，但仍在寻找有效靶点分子以促进轴突再生。尽管在描述参与轴突再生的促再生因子方面已经有了重大的历史进展，但对内在抑制剂的研究相对较新。EFA6（ARF6 的交换因子）已被证明可抑制不同生物体中的轴突再生。EFA6 抑制可能是一种有前途的治疗策略，可促进轴突损伤后轴突的再生和功能恢复。本综述总结了通过调节微管动力学和影响 ARF6（ADP-ribosylation factor 6）GTPase 介导的整合素运输，EFA6 抑制在轴突再生中的抑制作用。
