Inhibition of Kinesin-5, a microtubule-based motor protein, as a strategy for enhancing regeneration of adult axons.
Inhibition of Kinesin-5, a microtubule-based motor protein, as a strategy for enhancing regeneration of adult axons.
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DOI：
10.1111/j.1600-0854.2010.01152.x
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Baas PW
中科院分区：
文献类型：
--
作者：
Lin S;Liu M;Son YJ;Timothy Himes B;Snow DM;Yu W;Baas PW
发育中的神经元表达一种称为驱动蛋白-5（也称为kif 11或Eg 5）的运动蛋白，它在轴突生长期间对微管阵列的前进起到“刹车”的作用。对驱动蛋白-5的药理学抑制导致发育中的轴突以更快的速率生长，更少地缩回，并且生长超过否则会导致其转向的线索。在这里，我们证明，驱动蛋白-5也表达在成年神经元，虽然在较低的水平比在发展。我们假设抑制驱动蛋白-5可能使成年轴突更好地再生，并克服与损伤相关的排斥分子。使用成年小鼠背根神经节神经元，我们发现抗驱动蛋白-5药物导致轴突生长更快，并以更高的频率与抑制性硫酸软骨素蛋白聚糖（CSPG）交叉。这些影响可能部分是由于微管运输效率的变化，沿着轴突轴以及增强微管进入轴突的远端。在某些情况下，当它们与其他已知的增强轴突再生的治疗方法结合使用时，观察到的药物效果会进一步增强。总的来说，这些结果表明，抗驱动蛋白-5药物可能是用于治疗神经损伤的工具库的有用补充。
Developing neurons express a motor protein called kinesin-5 (also called kif11 or Eg5) which acts as a “brake” on the advance of the microtubule array during axonal growth. Pharmacological inhibition of kinesin-5 causes the developing axon to grow at a faster rate, retract less, and grow past cues that would other wise cause it to turn. Here we demonstrate that kinesin-5 is also expressed in adult neurons, albeit at lower levels than during development. We hypothesized that inhibiting kinesin-5 might enable adult axons to regenerate better, and to overcome repulsive molecules associated with injury. Using adult mouse dorsal root ganglion neurons, we found that anti-kinesin-5 drugs cause axons to grow faster and to cross with higher frequency onto inhibitory chondroitin sulfate proteoglycans (CSPGs). These effects may be due in part to changes in the efficiency of microtubule transport along the axonal shaft as well as enhanced microtubule entry into the distal tip of the axon. Effects observed with the drugs are further enhanced in some cases when they are used in combination with other treatments known to enhance axonal regeneration. Collectively, these results indicate that anti-kinesin-5 drugs may be a useful addition to the arsenal of tools used to treat nerve injury.
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DOI：
10.1083/jcb.200407191
发表时间：
2005-02-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
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DOI：
10.1016/j.cub.2008.11.021
发表时间：
2008-12-23
期刊：
Current biology : CB
影响因子：
--
作者：
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通讯作者：
Baas PW