While the peripheral nervous system is able to repair itself following injury and disease, recovery is often slow and incomplete, with no available treatments to enhance the effectiveness of regeneration. Using knock-out and transgenic overexpressor mice, we previously reported that BACE1, an aspartyl protease, as reported by Hemming et al. (PLoS One 4:12, 2009), negatively regulates peripheral nerve regeneration. Here, we investigated whether pharmacological inhibition of BACE may enhance peripheral nerve repair following traumatic nerve injury or neurodegenerative disease. BACE inhibitor-treated mice had increased numbers of regenerating axons and enhanced functional recovery after a sciatic nerve crush while inhibition increased axonal sprouting following a partial nerve injury. In the SOD1^G93A ALS mouse model, BACE inhibition increased axonal regeneration with improved muscle re-innervation. CHL1, a BACE1 substrate, was elevated in treated mice and may mediate enhanced regeneration. Our data demonstrates that pharmacological BACE inhibition accelerates peripheral axon regeneration after varied nerve injuries and could be used as a potential therapy.

虽然周围神经系统能够在受伤和患病后进行自我修复，但恢复往往缓慢且不完全，并且没有可用的治疗方法来增强再生的有效性。使用敲除和转基因过表达小鼠，我们之前报道了 BACE1，一种天冬氨酰蛋白酶，正如 Hemming 等人报道的那样。(PLoS One 4:12, 2009)，负调节周围神经再生。在这里，我们研究了 BACE 的药理抑制是否可以增强创伤性神经损伤或神经退行性疾病后的周围神经修复。BACE抑制剂治疗的小鼠在坐骨神经挤压后再生轴突的数量增加，功能恢复增强，而抑制则增加了部分神经损伤后的轴突萌芽。在 SOD1 ^G93A ALS 小鼠模型中，BACE 抑制可增加轴突再生，改善肌肉重新神经支配。CHL1（一种 BACE1 底物）在治疗小鼠中升高，可能介导增强的再生。我们的数据表明，药理学 BACE 抑制可加速各种神经损伤后的外周轴突再生，可作为一种潜在的治疗方法。