Dong Xiong, Hong Hongxiang, Cui Zhiming
Department of Spinal Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Exp Ther Med. 2023 Oct 3;26(5):541. doi: 10.3892/etm.2023.12240. eCollection 2023 Nov.
Spinal cord injury (SCI) is a major social problem with a heavy burden on patient physiology and psychology. Glial scar formation and irreversible neuron loss are the two key points during SCI progression. During the acute phase of spinal cord injury, glial scars form, limiting the progression of inflammation. However, in the subacute or chronic phase, glial scarring inhibits axon regeneration. Following spinal cord injury, irreversible loss of neurons leads to further aggravation of spinal cord injury. Several therapies have been developed to improve either glial scar or neuron loss; however, few therapies reach the stage of clinical trials and there are no mainstream therapies for SCI. Exploring the key mechanism of SCI is crucial for finding further treatments. Glycogen synthase kinase-3 (GSK-3) is a widely expressed kinase with important physiological and pathophysiological functions . Dysfunction of the GSK-3 signaling pathway during SCI has been widely discussed for controlling neurite growth and , improving the proliferation and neuronal differentiation of endogenous neural stem cells and functional recovery from spinal cord injury. SCI can decrease the phosphorylated (p)/total (t)-GSK-3β ratio, which leads to an increase in apoptosis, whereas treatment with GSK-3 inhibitors can promote neurogenesis. In addition, several therapies for the treatment of SCI involve signaling pathways associated with GSK-3. Furthermore, signaling pathways associated with GSK-3 also participate in the pathological process of neuropathic pain that remains following SCI. The present review summarized the roles of GSK-3 signaling in SCI to aid in the understanding of GSK-3 signaling during the pathological processes of SCI and to provide evidence for the development of comprehensive treatments.
脊髓损伤（SCI）是一个重大的社会问题，给患者的生理和心理带来沉重负担。胶质瘢痕形成和不可逆的神经元丢失是脊髓损伤进展过程中的两个关键点。在脊髓损伤的急性期，胶质瘢痕形成，限制了炎症的进展。然而，在亚急性或慢性期，胶质瘢痕形成会抑制轴突再生。脊髓损伤后，神经元的不可逆丢失会导致脊髓损伤进一步加重。已经开发了几种疗法来改善胶质瘢痕或神经元丢失；然而，很少有疗法进入临床试验阶段，并且目前还没有治疗脊髓损伤的主流疗法。探索脊髓损伤的关键机制对于寻找进一步的治疗方法至关重要。糖原合酶激酶-3（GSK-3）是一种广泛表达的激酶，具有重要的生理和病理生理功能。脊髓损伤期间GSK-3信号通路的功能障碍在控制神经突生长、改善内源性神经干细胞的增殖和神经元分化以及脊髓损伤后的功能恢复方面已被广泛讨论。脊髓损伤会降低磷酸化（p）/总（t）-GSK-3β比值，从而导致细胞凋亡增加，而用GSK-3抑制剂治疗可以促进神经发生。此外，几种治疗脊髓损伤的疗法涉及与GSK-3相关的信号通路。此外，与GSK-3相关的信号通路也参与了脊髓损伤后残留的神经性疼痛的病理过程。本综述总结了GSK-3信号在脊髓损伤中的作用，以帮助理解脊髓损伤病理过程中的GSK-3信号，并为综合治疗的发展提供证据。
