Sengottuvel Vetrivel, Fischer Dietmar
Department of Experimental Neurology; Heinrich-Heine University of Düsseldorf; Düsseldorf, Germany.
Commun Integr Biol. 2011 Jul;4(4):391-3. doi: 10.4161/cib.4.4.15552. Epub 2011 Jul 1.
Traumatic CNS injuries often cause permanent, devastating disabilities due to a lack of regeneration of damaged axons. Next to an insufficient intrinsic capability of CNS neurons to regrow axons, also inhibitory molecules that are associated with the CNS myelin and the glial scar contribute to the failure of axonal regeneration. Strategies targeting the inhibitory molecules, their receptors or downstream signaling pathways result in little improvement of regeneration in vivo. However, the combination of such approaches together with measures that increase the intrinsic growth potential of neurons reportedly lead to a significantly better outcome. In this mini-review we outline and discuss a novel therapeutic strategy facilitating axon regeneration by directly targeting microtubule dynamics in axonal growth cones and reducing the inhibitory scar formation at the injury site by the anticancer drug Taxol. Moreover, we portray the mechanisms underlying the beneficial effects of Taxol and its potential as an adjuvant drug to accomplish substantial regeneration and functional recovery after CNS injuries in vivo.
创伤性中枢神经系统损伤常常由于受损轴突缺乏再生能力而导致永久性的、严重的残疾。除了中枢神经系统神经元轴突再生的内在能力不足外,与中枢神经系统髓鞘和胶质瘢痕相关的抑制分子也导致了轴突再生的失败。针对抑制分子、其受体或下游信号通路的策略在体内对再生的改善甚微。然而,据报道,将这些方法与提高神经元内在生长潜力的措施相结合会带来明显更好的结果。在这篇综述中,我们概述并讨论了一种新的治疗策略,即通过直接靶向轴突生长锥中的微管动力学来促进轴突再生,并通过抗癌药物紫杉醇减少损伤部位的抑制性瘢痕形成。此外,我们描述了紫杉醇有益作用的潜在机制及其作为辅助药物在体内实现中枢神经系统损伤后实质性再生和功能恢复的潜力。