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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma.
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MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma.

机译：MAG和OMgp与Nogo-A协同作用，以限制脊髓损伤后的轴突生长和神经功能恢复。

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Functional recovery after adult CNS damage is limited in part by myelin inhibitors of axonal regrowth. Three molecules, Nogo-A, MAG, and OMgp, are produced by oligodendrocytes and share neuronal receptor mechanisms through NgR1 and PirB. While each has an axon-inhibitory role in vitro, their in vivo interactions and relative potencies have not been defined. Here, we compared mice singly, doubly, or triply mutant for these three myelin inhibitor proteins. The myelin extracted from Nogo-A mutant mice is less inhibitory for axons than is that from wild-type mice, but myelin lacking MAG and OMgp is indistinguishable from control. However, myelin lacking all three inhibitors is less inhibitory than Nogo-A-deficient myelin, uncovering a redundant and synergistic role for all three proteins in axonal growth inhibition. Spinal cord injury studies revealed an identical in vivo hierarchy of these three myelin proteins. Loss of Nogo-A allows corticospinal and raphespinal axon growth above and below the injury, as well as greater behavioral recovery than in wild-type or heterozygous mutant mice. In contrast, deletion of MAG and OMgp stimulates neither axonal growth nor enhanced locomotion. The triple-mutant mice exhibit greater axonal growth and improved locomotion, consistent with a principal role for Nogo-A and synergistic actions for MAG and OMgp, presumably through shared receptors. These data support the hypothesis that targeting all three myelin ligands, as with NgR1 decoy receptor, provides the optimal chance for overcoming myelin inhibition and improving neurological function.
机译：成人中枢神经系统损伤后的功能恢复部分受到轴突再生的髓磷脂抑制剂的限制。少突胶质细胞产生三种分子Nogo-A，MAG和OMgp，它们通过NgR1和PirB共享神经元受体机制。尽管它们在体外均具有轴突抑制作用，但它们的体内相互作用和相对效能尚未确定。在这里，我们比较了这三种髓磷脂抑制剂蛋白的小鼠单，双或三突变体。与野生型小鼠相比，从Nogo-A突变小鼠中提取的髓磷脂对轴突的抑制作用较小，但是缺乏MAG和OMgp的髓磷脂与对​​照却没有区别。但是，缺乏这三种抑制剂的髓磷脂的抑制作用要比Nogo-A缺陷型髓鞘的抑制作用小，从而揭示了这三种蛋白在轴突生长抑制中的冗余和协同作用。脊髓损伤研究显示这三种髓磷脂蛋白在体内具有相同的层次。与野生型或杂合突变小鼠相比，Nogo-A的缺失使皮质脊髓和短尾轴突的轴突生长在损伤的上方和下方，并且行为恢复更大。相反，删除MAG和OMgp既不会刺激轴突生长，也不会刺激运动。三突变体小鼠表现出更大的轴突生长和改善的运动，这与Nogo-A的主要作用以及MAG和OMgp的协同作用（大概是通过共享受体）一致。这些数据支持以下假设：与NgR1诱饵受体一样，靶向所有三个髓磷脂配体可提供克服髓磷脂抑制和改善神经功能的最佳机会。

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