After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS.

中文翻译：

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通过恢复雪旺细胞 c-Jun 可以挽救因衰老或慢性去神经支配而导致的神经再生失败


神经损伤后，髓磷脂和雷马克雪旺细胞重新编程以修复专门用于再生的细胞。这些细胞通常提供强大的再生支持，但在衰老的动物中以及由于轴突生长缓慢而导致的慢性去神经过程中会失效。这会损害轴突再生并导致严重的临床问题。在小鼠中，我们发现修复细胞表达的 c-Jun 蛋白减少，因为这些细胞提供的再生支持在衰老和慢性去神经支配过程中下降。在这两种情况下，通过基因恢复雪旺细胞 c-Jun 水平可以将再生恢复到控制水平。我们确定了介导这种效应的潜在候选基因，并表明 Shh 参与了雪旺细胞 c-Jun 水平的控制。这确立了一种共同机制，即雪旺细胞中 c-Jun 的减少，在衰老和慢性去神经支配过程中调节神经修复的成功和失败。这为解决重要的临床问题提供了一个分子框架，提出了可以靶向促进 PNS 修复的分子途径。