脊髓损伤(SCI)是医学研究中的一个持续挑战,也是一个全球性的治疗问题。这种情况的治疗在临床实践中仍然困难。因此,预防,治疗,SCI的康复已成为医学领域迫在眉睫的任务。
最近的证据表明Wnt/β-catenin信号通路的重要作用,典型的Wnt信号通路,在神经发育中,轴突引导,神经性疼痛缓解,和神经元存活。Wnt-3a被认为是经典Wnt信号通路的激活剂。这种激活剂在背侧中线区域表达,并负责脊髓发育。此外,Wnt-3a在自噬中起调节作用,凋亡,和神经元再生;神经源性炎症;和轴突再生。在这里,我们证明SCI后神经元自噬受Wnt-3a通过β-catenin和哺乳动物雷帕霉素靶信号通路调节。我们的研究还发现,Wnt-3a为SCI后神经功能的恢复提供了有利的微环境。关键信息:本研究系统阐述了Wnt-3a在SCI后的神经保护作用及其神经保护分子机制。本研究为SCI的临床治疗提供了新的分子机制和研究依据。
Spinal cord injury (SCI) is a constant challenge in medical research and a global therapeutic problem. Treatment of this condition remains difficult in clinical practice. Hence, prevention, treatment, and rehabilitation of SCI have become imminent tasks in the medical field.
Recent evidence suggest the important role of Wnt/β-catenin signaling pathway, a canonical Wnt signaling pathway, in neural development, axon guidance, neuropathic pain relief, and neuronal survival. Wnt-3a is regarded as an activator of the canonical Wnt signaling pathway. This activator is expressed in the dorsal midline region and is responsible for spinal cord development. In addition, Wnt-3a plays a regulatory role in autophagy, apoptosis, and regeneration of neurons; neurogenic inflammation; and axon regeneration. Herein, we demonstrated that neuronal autophagy was regulated by Wnt-3a via β-catenin and mammalian target of rapamycin signaling pathways after SCI. Our study also discovered that the Wnt-3a provided a favorable microenvironment for the recovery of nerve function after SCI. Key Messages: This study systematically elaborates the neuroprotective effect of Wnt-3a and its neuroprotection molecular mechanism after SCI. This study provides a new molecular mechanism and research basis for clinical treatment of SCI.