Guillain-Barré syndrome is an autoimmune peripheral neuropathy and a common cause of neuromuscular paralysis. Preceding infection induces the production of anti-ganglioside (GD) antibodies attacking its own peripheral nerves. Damaged axons fail to regrow and to re-innervate target muscles. In severe peripheral nerve injuries (PNI) such as proximal PNIs that requires long-distance axon regeneration, motor functional recovery is virtually non-exist. In mice, regenerating axons must reach target muscle within 35 days (critical period) to reform functional neuromuscular junctions and regain motor function. In current study, forced expression of human heat shock protein (hHsp) 27 completely reversed anti-GD-induced deleterious effects on nerve repair assessed by animal behavioral assays, electrophysiology and histology studies, and the beneficial effect was validated in a second mouse line of hHsp27. Protective effect of hHsp27 on prolonged muscle denervation was examined by performing repeated sciatic nerve crushes to delay regenerating axons from reaching distal muscle from 37 days up to 55 days. Strikingly, hHsp27 was able to extend the critical period of motor functional recovery for up to 55 days, and preserved the integrity of axons and mitochondria in distal nerves. Taken together, current study provides insight into the therapeutic potential of Hsp27 for nerve repair by enhancing muscle receptiveness to regenerating axons.

中文翻译：

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热休克蛋白是自身免疫性周围神经病和严重周围神经损伤中神经修复的关键治疗靶点

格林-巴利综合征是一种自身免疫性周围神经病变，也是神经肌肉麻痹的常见原因。感染前诱导产生攻击自身周围神经的抗神经节苷脂 (GD) 抗体。受损的轴突无法再生和重新支配目标肌肉。在需要长距离轴突再生的近端 PNI 等严重周围神经损伤 (PNI) 中，几乎不存在运动功能恢复。在小鼠中，再生轴突必须在 35 天（关键期）内到达目标肌肉，以改造功能性神经肌肉接头并恢复运动功能。在目前的研究中，人类热休克蛋白 (hHsp) 27 的强制表达完全逆转了通过动物行为测定、电生理学和组织学研究评估的抗 GD 诱导的对神经修复的有害影响，并且有益效果在 hHsp27 的第二个小鼠系中得到验证。hHsp27 对延长肌肉去神经支配的保护作用通过反复进行坐骨神经挤压以延迟再生轴突从 37 天到 55 天到达远端肌肉来检查。引人注目的是，hHsp27 能够将运动功能恢复的关键期延长长达 55 天，并保持远端神经中轴突和线粒体的完整性。总之，目前的研究通过增强肌肉对再生轴突的接受能力，深入了解 Hsp27 对神经修复的治疗潜力。hHsp27 对延长肌肉去神经支配的保护作用通过反复进行坐骨神经挤压以延迟再生轴突从 37 天到 55 天到达远端肌肉来检查。引人注目的是，hHsp27 能够将运动功能恢复的关键期延长长达 55 天，并保持远端神经中轴突和线粒体的完整性。总之，目前的研究通过增强肌肉对再生轴突的接受能力，深入了解 Hsp27 对神经修复的治疗潜力。hHsp27 对延长肌肉去神经支配的保护作用通过反复进行坐骨神经挤压以延迟再生轴突从 37 天到 55 天到达远端肌肉来检查。引人注目的是，hHsp27 能够将运动功能恢复的关键期延长长达 55 天，并保持远端神经中轴突和线粒体的完整性。总之，目前的研究通过增强肌肉对再生轴突的接受能力，深入了解 Hsp27 对神经修复的治疗潜力。