Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (4): 1409-1427.doi: 10.4103/NRR.NRR-D-24-01507

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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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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