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mTOR 通路:脊髓损伤的潜在治疗靶点。

mTOR pathway: A potential therapeutic target for spinal cord injury.

机构信息

Department of Spine Surgery, Ganzhou People's Hospital, 16 Meiguan Avenue, Ganzhou 342800, PR China; The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou 342800, PR China.

出版信息

Biomed Pharmacother. 2022 Jan;145:112430. doi: 10.1016/j.biopha.2021.112430. Epub 2021 Nov 17.

Abstract

Spinal cord injury (SCI) is the most common disabling spinal injury, and the complex pathological process can eventually lead to severe neurological dysfunction. Many studies have reported that the mammalian target of rapamycin (mTOR) signaling pathway plays an important role in synaptogenesis, neuron growth, differentiation, and survival after central nervous system injury. It is also involved in various traumatic and central nervous system diseases, including traumatic brain injury, neonatal hypoxic-ischemic brain injury, Alzheimer's disease, Parkinson's disease, and cerebral apoplexy. mTOR has also been reported to play an important regulatory role in various pathophysiological processes following SCI. Activation of mTOR signals after SCI can regulate physiological and pathological processes, such as proliferation and differentiation of neural stem cells, regeneration of nerve axons, neuroinflammation, and glial scar formation, through various pathways. Inhibition of mTOR activity has been confirmed to promote repair in SCI. At present, many studies have reported that Chinese herbal medicine can inhibit the SCI-activated mTOR pathway to improve the microenvironment and promote nerve repair after SCI. Due to the role of the mTOR pathway in SCI, it may be a potential therapeutic target for SCI. This review is focused on the pathophysiological process of SCI, characteristics of the mTOR pathway, role of the mTOR pathway in SCI, role of inhibition of mTOR on SCI, and role and significance of inhibition of mTOR by related Chinese herbal medicine inhibitors in SCI. In addition, the review discusses the deficiencies and solutions to mTOR and SCI research shortcomings. This study hopes to provide reference for mTOR and SCI research and a theoretical basis for SCI biotherapy.

摘要

脊髓损伤(SCI)是最常见的致残性脊髓损伤,其复杂的病理过程最终可导致严重的神经功能障碍。许多研究报道哺乳动物雷帕霉素靶蛋白(mTOR)信号通路在中枢神经系统损伤后的突触形成、神经元生长、分化和存活中发挥重要作用。它还涉及各种创伤性和中枢神经系统疾病,包括创伤性脑损伤、新生儿缺氧缺血性脑损伤、阿尔茨海默病、帕金森病和中风。mTOR 还被报道在 SCI 后各种病理生理过程中发挥重要的调节作用。SCI 后 mTOR 信号的激活可以通过多种途径调节神经干细胞的增殖和分化、神经轴突的再生、神经炎症和胶质瘢痕形成等生理和病理过程。抑制 mTOR 活性已被证实可促进 SCI 修复。目前,许多研究报道中药可抑制 SCI 激活的 mTOR 通路,改善 SCI 后的微环境,促进神经修复。鉴于 mTOR 通路在 SCI 中的作用,它可能是 SCI 的潜在治疗靶点。本综述重点介绍了 SCI 的病理生理过程、mTOR 通路的特征、mTOR 通路在 SCI 中的作用、抑制 mTOR 对 SCI 的作用以及相关中药抑制剂抑制 mTOR 在 SCI 中的作用和意义。此外,该综述还讨论了 mTOR 和 SCI 研究中的不足及解决方案。本研究希望为 mTOR 和 SCI 研究提供参考,并为 SCI 生物治疗提供理论依据。

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