中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (10): 1602-1603.doi: 10.4103/1673-5374.167753

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

维持糖原合酶激酶-3活性有助于损伤周围神经再生?

  

  • 收稿日期:2015-09-08 出版日期:2015-10-28 发布日期:2015-10-28

Role of GSK3 in peripheral nerve regeneration

Heike Diekmann, Dietmar Fischer*   

  1. Division of Experimental Neurology, Department of Neurology,
    Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany
  • Received:2015-09-08 Online:2015-10-28 Published:2015-10-28
  • Contact: Dietmar Fischer, Ph.D.,dietmar.fischer@hhu.de.

摘要:

糖原合成激酶3(GSK3)作为一种多功能的丝氨酸/苏氨酸蛋白激酶,通过其多元化的活性调节方式,参与神经发育及修复过程。在神经退行性疾病等多种重大疾病的研究中,选择其作为治疗靶点,受到越来越多研究者的重视。虽然GSK3是无可争议地调节轴突损伤再生过程,但它所起到的作用仍存在争议。有学者认为,GSK3抑制促进轴突生长/再生,而另一些报道恰恰相反。作者假设增加微管动力学可能不利于遇到抑制环境中(微管-脱聚合化)的中枢神经系统轴突再生。因此,GSK3S/ A对中枢神经系统轴突再生是微不足道的,当然,此观点需要进一步的实验验证。当然,由于GSK3信号传导的复杂性,在未来研究中可得到更为有趣的特性,也有可能为神经损伤提供新的治疗方案。

Abstract:

GSK3 phosphorylation reportedly supports regeneration-promoting gene transcription (e.g., SMAD expression). Therefore, opposing GSK3 regulation in different neuronal compartments (e.g., soma vs. growth cone) or direct manipulation of downstream GSK3 targets instead of GSK3 itself may further increase the regenerative response in comparison to globally increased GSK3 activity. Finally, it needs to be investigated whether GSK3 DKI mice show improved axon regeneration also in the CNS. We envisage that increased microtubule dynamics might be rather unfavorable for regenerating axons that encounter an inhibitory (thus microtubule-depolymerizing) environment as in the CNS. Therefore, negligible or even opposite effects of GSK3S/A on CNS axonal regeneration are equally expectable and further experiments are required to address these possibilities. Surely, the complexity of GSK3 signaling will provide more interesting features in the future, which could then potentially be developed into novel therapeutic treatment options for nerve injuries.