Inactivation of Rho signaling pathway promotes CNS axon regeneration
Inactivation of Rho signaling pathway promotes CNS axon regeneration
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DOI：
10.1523/jneurosci.19-17-07537.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
McKerracher, L
中科院分区：
文献类型：
--
作者：
Lehmann, M;Fournier, A;McKerracher, L
中枢神经系统的再生被许多不同的生长抑制蛋白阻断。为了促进再生，我们研究了一种阻断神经元对生长抑制信号反应的策略。在这里，我们报道当Rho GTPase失活时，受损的轴突直接在复杂的抑制底物上再生。用C3酶处理PC12细胞使Rho失活，并转染显性负Rho，使神经突起在抑制性底物上生长。用髓磷脂相关糖蛋白和髓磷脂底物上的C3延伸神经突治疗原发性视网膜神经元。为了探索视神经在体内的再生，我们粉碎了成年大鼠的视神经。C3治疗后，许多切割的轴突穿过病变，在视神经远端白质中重新生长。这些结果表明，靶向趋同于Rho的信号机制可以刺激抑制性中枢神经系统底物上的轴突再生。
Regeneration in the CNS is blocked by many different growth inhibitory proteins. To foster regeneration, we have investigated a strategy to block the neuronal response to growth inhibitory signals. Here, we report that injured axons regrow directly on complex inhibitory substrates when Rho GTPase is inactivated. Treatment of PC12 cells with C3 enzyme to inactivate Rho and transfection with dominant negative Rho allowed neurite growth on inhibitory substrates. Primary retinal neurons treated with C3 extended neurites on myelin-associated glycoprotein and myelin substrates. To explore regeneration in vivo, we crushed optic nerves of adult rat. After C3 treatment, numerous cut axons traversed the lesion to regrow in the distal white matter of the optic nerve. These results indicate that targeting signaling mechanisms converging to Rho stimulates axon regeneration on inhibitory CNS substrates.