中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (4): 1409-1427.doi: 10.4103/NRR.NRR-D-24-01507

• 综述:退行性病与再生 • 上一篇    下一篇

线粒体靶向干预慢性神经退行性疾病的内在潜力

  

  • 出版日期:2026-04-15 发布日期:2025-07-25
  • 基金资助:
    延安大学秦川川 “科学家+工程师 ”团队专项基金（2023KXJ-012号）、延安大学科技成果转化基金（2023CGZH-001）、大学生创新创业训练计划延安大学科技成果转化基金（2023CGZH-001）；大学生创新创业训练计划项目（D2023158、2024D2023158、2024D2023158、2024D2023158、2024D2023158、2024D2023158。 D2023158, 202410719056）；延安大学生产培养项目（CXY202001）；贵州茅台酒厂医院科研与人才发展基金项目（CXY202001）；人才发展基金项目（MTyk2022-25）。

Inherent potential of mitochondria-targeted interventions for chronic neurodegenerative diseases

Min Zhou1, #, Min Zheng1, #, Siyao Liang1, #, Maomao Li1 , Jiarui Ma1 , Shiyu Zhang1 , Xinyao Song1 , Yonglin Hu2 , Yuhong Lyu1, *, Xingkun Ou2, *, Changwu Yue1, 3, *   

  1. 1 Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, Yan’an Medical College of Yan’an University, Yan’an, Shaanxi Province, China;  2 Department of Laboratory Medicine, Kweichow Moutai Hospital, Zunyi, Guizhou Province, China;  3 Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yan’an University, Yan’an, Shaanxi Province, China
  • Online:2026-04-15 Published:2025-07-25
  • Contact: Yuhong Lyu, MS, yuhonglyu@126.com; Xingkun Ou, MS, ouxkun@163.com; Changwu Yue, DS, changwuyue@yau.edu.cn.
  • Supported by:
    This work was partly supported by the Yan’an University Qin Chuanyuan “Scientist + Engineer” Team Special Fund, No. 2023KXJ-012 (to YL); Yan’an University Transformation of Scientific and Technological Achievements Fund, No. 2023CGZH-001 (to YL); College Students Innovation and Entrepreneurship Training Program, Nos. D2023158, 202410719056 (to XS, JM); Yan’an University Production and Cultivation Project, No. CXY202001 (to YL); Kweichow Moutai Hospital Research and Talent Development Fund Project, No. MTyk2022-25 (to XO).

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摘要：

慢性神经退行性疾病的治愈率很低，人们急需寻找更好的干预方法。近年来，许多研究表明，可以通过改善线粒体功能障碍来干预慢性神经退行性疾病。文章的目的是综述线粒体功能障碍与慢性神经退行性疾病的关系和机制，旨在揭示线粒体靶向干预慢性神经退行性疾病的内在潜力，寻找更多可行的新疗法。文章详细综述了针对慢性神经退行性疾病的线粒体靶向干预方法，包括促进线粒体自噬、抑制线粒体分裂、促进线粒体生物生成、针对线粒体的抗氧化剂、线粒体移植，这些方法各有其独特的优势和潜在的局限性，适用于不同的慢性神经退行性疾病治疗策略。促进线粒体吞噬和抑制线粒体分裂可能对延缓疾病进展特别有效，尤其是在疾病的早期阶段。促进线粒体生物生成和靶向线粒体抗氧化剂可提高细胞的抗氧化能力和能量代谢，从而在疾病的中期阶段提供更多的治疗益处。线粒体移植作为一种新兴的治疗方法，目前仍处于实验阶段，但其恢复受损细胞功能的潜力巨大。未来的研究应进一步探索这些干预方法的机制和效果，特别是其在临床应用中的安全性和有效性。此外，通过基因编辑技术或纳米技术等开发新的靶向线粒体干预策略，可能会为慢性神经退行性疾病的治疗提供更具创新性的解决方案。同时，整合多种干预方法的联合治疗策略也可能是改善治疗效果的有效途径。

https://orcid.org/0000-0003-1859-2457 (Yuhong Lyu); https://orcid.org/0000-0003-2208-9686 (Xingkun Ou); 

https://orcid.org/0000-0003-2679-5772 (Changwu Yue)

关键词: 阿尔茨海默病, 肌萎缩侧索硬化, 钙平衡, 氧化应激, 亨廷顿氏病, 线粒体功能障碍, 线粒体, 膜渗透性转换孔(mPTP), 嗜硝细胞吞噬, 神经退行性疾病, 帕金森病, 靶向治疗, 干预策略

Abstract: The cure rate for chronic neurodegenerative diseases remains low, creating an urgent need for improved intervention methods. Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases. This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases, aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options. We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, applying mitochondria-targeting antioxidants, and transplanting mitochondria. Each method has unique advantages and potential limitations, making them suitable for various therapeutic situations. Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression, especially in the early stages. In contrast, those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism. Mitochondrial transplantation, while still experimental, holds great promise for restoring the function of damaged cells. Future research should focus on exploring the mechanisms and effects of these intervention strategies, particularly regarding their safety and efficacy in clinical settings. Additionally, the development of innovative mitochondria-targeting approaches, such as gene editing and nanotechnology, may provide new solutions for treating chronic neurodegenerative diseases. Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, calcium homeostasis, oxidative stress, Huntington’s disease, mitochondrial dysfunction, mitochondria, mitophagy, neurodegenerative diseases, Parkinson’s disease, targeted therapy