中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (13): 1265-1266.doi: 10.4103/1673-5374.137572

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

以微管为基础的治疗策略促进损伤神经再生

  

  • 收稿日期:2014-06-27 出版日期:2014-07-11 发布日期:2014-07-11

Beyond taxol: microtubule-based strategies for promoting nerve regeneration after injury

Peter W. Baas   

  1. Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA, USA
  • Received:2014-06-27 Online:2014-07-11 Published:2014-07-11
  • Contact: Peter W. Baas, Ph.D., Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA, pbaas@drexelmed.edu.

摘要:

神经组织损伤后,损伤轴突会具有再生能力,但其再生能力是相当有限的,尤其是中枢神经系统轴突。这是因为受损的轴突往往会回缩,因为它们会遇到一些阻碍因素,如瘢痕组织和抑制性分子,还因为它们的生长率与新生的轴突根本不匹配。来自美国德雷克塞尔大学Peter W. Baas教授关注微管治疗,并将其作为成年轴突损伤后再生的最重要因素之一。微管是一种中空聚合物纤维丝,由微管蛋白亚基组成进而支撑轴突结构。除了其结构上的作用,对许多负责细胞内运输的分子运动蛋白来说微管也是一种重要基质。微管在本质上是极性结构,通过自身具有的“加”、“减”终端能力而备受亲睐。在轴突中,将微管对准成轴向平行的阵列,并在微管两端加上导离体细胞,从而建立方向性与不同运动传输系统,微管聚集并进入轴突,然后在形成分支点再次分开,并存在于轴突尖端的生长锥内部。微管具有的相关轴突生长和再生的能力,与上述提到的所有因素有关。此外,微管的动态特性是极为重要的,尤其在轴突远端,对于轴突形成一个可行的生长锥,正常响应外部信号很有帮助。

Abstract:

After injury, damaged axons have the capacity to regenerate, but the regenerative capacity of the axon, particularly axons of the central nervous system, is quite limited. This is because the damaged axons tend to retract, because they encounter obstacles such as scar tissue and inhibitory molecules, and because their growth rates simply do not match those of a juvenile axon. Prof. Peter W. Baas from Drexel University, USA focus on microtubules as among the most important factors in encouraging injured adult axons to regenerate. Microtubules are hollow polymeric filaments composed of tubulin subunits that provide structural support for the axon. In addition to their structural role, microtubules are an important substrate for many of the molecular motor proteins responsible for intracellular transport. Microtubules are intrinsically polar structures, with their "plus" ends favored for assembly over their "minus" ends. Molecular motor proteins interact with cargo such as membranous organelles that are transported in conjunction with the motor. In the axon, the microtubules are aligned into a paraxial array with the plus ends of the microtubules directed away from the cell body, thus establishing the directionality with which different motors convey their cargo. Microtubules gather together and funnel into the hillock region of the axon and then splay apart again at sites of branch formation and within the growth cone at the tip of the elongating axon. Microtubules are relevant to axonal growth and regeneration for reasons related to all of these factors. Additionally, it appears that the dynamic properties of microtubules are critically important especially in the distal tip of the axon, for the capacity of the axon to form a viable growth cone, to turn properly in response to external cues, and to grow with the vitality typical of the developing nervous system.