基于Wnt/β-catenin经典信号通路及相关蛋白表达对脊髓损伤及其治疗的机制探讨
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上海中医药大学附属上海市中西医结合医院

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上海市科学技术委员会科研计划项目(15DZ1942606)


Study on the Mechanism of Spinal Cord Injury and Its Therapy Based on Classical Wnt/β-catenin Signal Pathway and Related Protein Expression
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    摘要:

    脊髓损伤(Spinal Cord Injury, SCI)是人类极具破坏性的创伤性疾病之一,是全球性的治疗难题。神经元损伤后难以再生,导致该疾病高致残率、死亡率,为家庭和社会带来巨大的经济负担。经典Wnt/β-连环蛋白(β-catenin)信号通路是SCI过程中至关重要的信号转导系统,当前研究证实多种外源性刺激如沉默信息调节因子2同源蛋白1(silent mating type information regulation 2 homolog 1, SIRT1/Sirtuin 1)、层粘连蛋白样蛋白(Netrin)、微小RNA(MicroRNA,miRNA)、热性休克蛋白(heat shock protein,HSP)等可激活该通路并调节下游靶基因的表达,从而减少SCI后脊髓神经元的自噬和凋亡,抑制炎症,促进神经细胞增殖以及轴突再生,减少瘢痕形成等,最终促进SCI修复。本文总结近3年来基于Wnt/β-catenin信号通路参与SCI保护的相关分子机制,以期为发现SCI新的治疗靶点提供思路。

    Abstract:

    Spinal cord injury (SCI) is one of the most destructive traumatic diseases of human beings. Meanwhile, it is a global treatment problem. It is difficult for neurons to regenerate after injury. SCI will lead to high disability rate and mortality rate which brings huge economic burden not only to the family and but also to society. The classical Wnt/ β-catenin signal pathway is an important signal transduction system during the process of SCI. Current studies have confirmed that a variety of exogenous stimuli, such as silencing information regulator 2 homologous protein 1 (SIRT1)、laminin-like protein (Netrin)、microRNA(miRNA)、heat shock protein(HSP), can activate this pathway and regulate the expression of downstream target genes. Hence, it is beneficial to reduce autophagy and apoptosis of spinal cord neurons after SCI, inhibit inflammation, promote nerve cell proliferation and axon regeneration, decrease scar formation, and finally realize the aim of repairing SCI. This article concludes the molecular mechanism of SCI protection based on Wnt/ β-catenin signaling pathway in recent 3 years, in order to provide ideas for discovering new therapeutic targets of SCI.

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  • 收稿日期:2021-10-30
  • 最后修改日期:2022-04-07
  • 录用日期:2022-04-08
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