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代谢重编程:脊髓损伤治疗的新选择

Metabolic reprogramming: a new option for the treatment of spinal cord injury.

作者信息

Chen Jiangjie, Chen Jinyang, Yu Chao, Xia Kaishun, Yang Biao, Wang Ronghao, Li Yi, Shi Kesi, Zhang Yuang, Xu Haibin, Zhang Xuesong, Wang Jingkai, Chen Qixin, Liang Chengzhen

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang Province, China.

出版信息

Neural Regen Res. 2025 Apr 1;20(4):1042-1057. doi: 10.4103/NRR.NRR-D-23-01604. Epub 2024 Apr 3.

Abstract

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

摘要

脊髓损伤给社会带来了显著的经济负担,主要是因为它们会导致严重的后遗症。尽管针对脊髓损伤的各种治疗方法不断发展,但其效果仍不尽人意。然而,对新陈代谢的深入理解以代谢重编程的形式开辟了新的治疗机会。在这篇综述中,我们探讨了脊髓损伤期间发生的代谢变化、其后果以及可用于代谢重编程的治疗手段。正常的脊髓代谢以独立的细胞代谢和细胞间代谢偶联为特征。然而,脊髓损伤会导致代谢紊乱,包括葡萄糖代谢、脂质代谢紊乱和线粒体功能障碍。这些代谢紊乱会导致相应的病理变化,包括轴突再生失败、瘢痕形成以及小胶质细胞活化。为了在代谢水平上挽救脊髓损伤,出现了潜在的代谢重编程方法,包括补充代谢底物、重建代谢偶联以及靶向线粒体治疗以改变细胞命运。现有证据表明,代谢重编程作为治疗脊髓损伤的下一代方法具有很大的前景。为了进一步推进脊髓损伤的代谢治疗,未来的努力应集中在更深入地理解神经代谢、开发更先进的代谢组学技术以及设计高效的代谢干预措施上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d44/11438339/512a1d1ed936/NRR-20-1042-g001.jpg

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