中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 845-849.doi: 10.4103/1673-5374.158351

• 综述:神经损伤修复保护与再生 •    下一篇

增强微管活性改善轴突再生:抑制驱动蛋白-5的作用

  

  • 收稿日期:2015-04-16 出版日期:2015-06-18 发布日期:2015-06-18

Inhibition of kinesin-5 improves regeneration of injured axons by a novel microtubule-based mechanism

Peter W. Baas, Andrew J. Matamoros   

  1. Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA, USA
  • Received:2015-04-16 Online:2015-06-18 Published:2015-06-18
  • Contact: Peter W. Baas, Ph.D., pbaas@drexelmed.edu.
  • Supported by:

    The work discussed here on kinesin-5 inhibition as a means for augmenting nerve regeneration after injury was supported mainly by grants from the Craig H. Neilsen Foundation.

摘要:

受损的成年轴突可以再生,但它们的再生能力是相当有限的,尤其是在中枢神经系统内。成人中枢神经系统中的受损轴突会趋于回缩或者变性,而不是再生。这是因为受损轴突遇到的物理和化学障碍,如瘢痕组织和损伤相关抑制分子,因为成人中枢神经系统环境通常富含的因子如髓鞘是不利于再生的,并且成人轴突固有的生长潜力与幼年轴突并不匹配。

Abstract:

Microtubules have been identified as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concerns that abnormally stabilizing microtubules may have only limited benefits for regeneration, while at the same time may be detrimental to the normal work that microtubules perform for the axon. Kinesin-5 (also called kif11 or Eg5), a molecular motor protein best known for its crucial role in mitosis, acts as a brake on microtubule movements by other motor proteins in the axon. Drugs that inhibit kinesin-5, originally developed to treat cancer, result in greater mobility of microtubules in the axon and an overall shift in the forces on the microtubule array. As a result, the axon grows faster, retracts less, and more readily enters environments that are inhibitory to axonal regeneration. Thus, drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost axonal regeneration without the concerns that accompany abnormal stabilization of the microtubule array. Even so, inhibiting kinesin-5 is not without its own caveats, such as potential problems with navigation of the regenerating axon to its target, as well as morphological effects on dendrites that could affect learning and memory if the drugs reach the brain.

Key words: microtubule, axon, kinesin-5, Eg5, regeneration, monastrol, molecular motor protein