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首页> 外文期刊>Neuron >ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS
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ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS

机译：ADF / Cofilin介导的actin周转促进成人CNS中的轴突再生

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摘要

Injured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss-and gain-of-function experiments followed by time-lapse microscopy, in vivo imaging, and whole-mount analysis show that axon regeneration is fueled by elevated actin turnover. Actin depolymerizing factor (ADF)/cofilin controls actin turnover to sustain axon regeneration after spinal cord injury through its actin-severing activity. This pinpoints ADF/cofilin as a key regulator of axon growth competence, irrespective of developmental stage. These findings reveal the central role of actin dynamics regulation in this process and elucidate a core mechanism underlying axon growth after CNS trauma. Thereby, neurons maintain the capacity to stimulate developmental programs during adult life, expanding their potential for plasticity. Thus, actin turnover is a key process for future regenerative interventions.
机译：受伤的轴突未能在成人CNS中再生，这与胚胎发育期间的剧烈增长形成鲜明对比。我们通过重新激活在发育过程中驱动神经元的形态发生转化的分子机制来探讨重新启动轴突延伸的潜力。遗传丧失和功能性实验，然后是延时显微镜，体内成像和全架分析表明，通过升高的肌动蛋白周转来促进轴突再生。肌动蛋白解聚因子（ADF）/ Cofilin对肌动蛋白转口进行控制，以通过其肌动蛋白切割活性损伤脊髓损伤后维持轴突再生。这种针对AADF / COFILIN作为轴突生长能力的关键调节器，无论发育阶段如何。这些发现揭示了肌动蛋白动力学调节在该过程中的核心作用，并阐明CNS创伤后轴突生长的核心机制。由此，神经元在成人寿命期间保持刺激发育计划的能力，扩大其可塑性的潜力。因此，actin周转是未来再生干预的关键过程。

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  • 来源
    《Neuron》 |2019年第6期|共19页
  • 作者

    Tedeschi Andrea; Dupraz Sebastian; Curcio Michele; Laskowski Claudia J.; Schaffran Barbara; Flynn Kevin C.; Santos Telma E.; Stern Sina; Hilton Brett J.; Larson Molly J. E.; Gurniak Christine B.; Witke Walter; Bradke Frank;

  • 作者单位

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

    Ohio State Univ Wexner Med Ctr Dept Neurosci Ctr Brain &

    Spinal Cord Repair 460 W 12th Ave;

    Univ Bonn Inst Genet Karlrobert Kreiten Str 13 D-53115 Bonn Germany;

    Univ Bonn Inst Genet Karlrobert Kreiten Str 13 D-53115 Bonn Germany;

    German Ctr Neurodegenerat Dis DZNE Axonal Growth &

    Regenerat Sigmund Freud Str 27 D-53127 Bonn;

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  • 正文语种 eng
  • 中图分类 神经病学;
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