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 (2): 648-658.doi: 10.4103/NRR.NRR-D-24-00848

• 综述:退行性病与再生 • 上一篇    下一篇

与年龄相关的髓鞘退行性变化是神经退行性疾病的初始危险因素吗？

  

  • 出版日期:2026-02-15 发布日期:2025-05-22

Is age-related myelinodegenerative change an initial risk factor of neurodegenerative diseases?

Shuangchan Wu1, 2, *, Jun Chen1, 3, *   

  1. 1 Sanhang Institute for Brain Science and Technology (SiBST), School of Medical Research, Northwestern Polytechnical University, Xi’an, Shaanxi Province, China;  2 Shenzhen Research Institute of Northwestern Polytechnical University, Shenzhen, Guangdong Province, China;  3 Institute for Biomedical Sciences of Pain, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China
  • Online:2026-02-15 Published:2025-05-22
  • Contact: Jun Chen, PhD, junchen_sibst@nwpu.edu.cn; Shuangchan Wu, PhD, wuxx@nwpu.edu.cn.
  • Supported by:
    This work was supported by grants from Guangdong Basic and Applied Basic Research Foundation, No. 2021A1515110801 (to SW); the National Natural Science Foundation of China, No. 82301511 (to SW); “Double First-Class” Construction Project of NPU, Nos. 0515023GH0202320 (to JC), 0515023SH0201320 (to JC) and 973 Program, No. 2011CB504100 (to JC).

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摘要：

髓鞘化，即神经轴突的连续鞘化，是神经系统中的一个生命周期过程，对于不同神经元间精确的时空传导动作电位至关重要。髓鞘还为轴突提供细胞间代谢支持。即使髓鞘完整性的轻微破坏，也会损害神经功能，增加神经系统疾病的易感性。事实上，髓鞘退行是一种公认的神经病理状态，与正常衰老和多种神经退行性疾病有关，如多发性硬化和阿尔茨海默病。在中枢神经系统中，致密髓鞘形成是由完全成熟的少突胶质细胞完成的，但随着大脑的衰老，整个少突胶质胶质细胞谱系都容易受到生物微环境等危险因素的影响。少突胶质细胞除了在动作电位传播中具有公认的功能外，还通过转移能量代谢产物和输送外泌体为轴突提供细胞间代谢支持。因此，衰老中枢神经系统内的髓鞘退行已成为神经退行性疾病发展的一个重要因素。干预措施可缓解与年龄相关的髓鞘变性，从而改善衰老个体的神经功能。因此，此次综述探讨了衰老过程中髓鞘的变化及其内在机制，以及衰老大脑髓鞘变性导致神经退行性疾病机制的最新进展，并分析了可能预防、减缓甚至逆转与年龄相关的髓鞘变性的可调节因素。未来的研究将深化对改善老年性髓鞘变性的理解，并将其视为延缓或预防神经退行性疾病的治疗靶点。

https://orcid.org/0000-0003-2637-8442 (Jun Chen); https://orcid.org/0000-0001-6140-0196 (Shuangchan Wu)

关键词: 白质, 少突胶质细胞, 髓鞘, 髓鞘轴突代谢产物串扰, 髓鞘退行, 衰老, 神经退行性疾病, 阿尔茨海默病, 帕金森病, 多发性硬化

Abstract: Myelination, the continuous ensheathment of neuronal axons, is a lifelong process in the nervous system that is essential for the precise, temporospatial conduction of action potentials between neurons. Myelin also provides intercellular metabolic support to axons. Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases. In fact, myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases, including multiple sclerosis and Alzheimer’s disease. In the central nervous system, compact myelin sheaths are formed by fully mature oligodendrocytes. However, the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages. In addition to their well-known role in action potential propagation, oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes. Therefore, myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases. Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals. In this review, we investigate the changes in myelin that are associated with aging and their underlying mechanisms. We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent, slow down, or even reverse age-related myelin degeneration. Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.

Key words: aging, Alzheimer’s disease, multiple sclerosis, myelin, myelin-axon metabolite crosstalk, myelinodegeneration, neurodegenerative disease, oligodendrocyte, Parkinson’s disease, white matter