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 (10): 4715-4728.doi: 10.4103/NRR.NRR-D-25-00101

• 综述:退行性病与再生 • 上一篇    下一篇

O-GlcNA酰化：连接大脑健康与神经退行性变的分子开关

  

  • 出版日期:2026-10-15 发布日期:2026-06-12

O-GlcNAcylation: A molecular switch linking brain health to neurodegeneration

Nan Shao1, #, Xiaoyan Zhang2, #, Yunzhi Ge1, Jiaxuan Tang1, Huawu Gao1, 3, *, Wenwen Si1, 3, *, Biao Cai1, 3, *   

  1. 1College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China; 
    2Department of Rehabilitation, the First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei, Anhui Province, China; 
    3Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui Province, China
  • Online:2026-10-15 Published:2026-06-12
  • Contact: Huawu Gao, MS, ghw2015@ahtcm.edu.cn; Wenwen Si, PhD, siwenwen2008@163.com; Biao Cai, PhD, caibiao@ahtcm.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82374553 (to BC), 82374209 (to WS); the Natural Science Foundation of Anhui Province, No. 2308085MH295 (to BC); the Natural Science Research Projects at Higher Institutions in Anhui Province, No. 2023AH050748 (to WS); the Scientific Research Planning Project in Anhui Province, No. 2022AH050485 (to HG); and the Quality Engineering Project in Anhui Province, No. 2023xscx096 (to NS).

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摘要：

神经退行性疾病通常是由有害的蛋白质积累和神经细胞损伤引起的。O连接N-乙酰氨基葡萄糖(O-GlcNAc)糖基化修饰是一种翻译后修饰，可通过调控蛋白质行为、细胞信号传导和能量平衡，在这些疾病中起着重要的调节作用。这种修饰是通过O-GlcNAc转移酶和O-GlcNAc酶的协同作用动态平衡的。此次综述揭示O-GlcNAc酰化将如何联系分子机制与神经退行性疾病以及靶向O-GlcNAc酰化治疗神经退行性疾病的前景。结果显示，在健康的大脑中，O-GlcNAc酰化有助于维持神经细胞的功能和存活，且其不平衡会导致疾病进展。值得注意的是，O-GlcNAc酰化的影响因疾病而异。在阿尔茨海默病中，其可阻断tau和Aβ等关键蛋白质的毒性变化。在帕金森病中，其可减少α-突触核蛋白的聚集，并可能会破坏多巴胺的产生。在肌萎缩侧索硬化中，其可保护神经纤维运输系统。此外，O-GlcNAc酰化在亨廷顿病、衰老、Machado-Joseph病、多发性硬化和巨轴突神经病的神经退行性疾病中也起着不可或缺的作用。针对O-GlcNAc酰化的新型疗法，如葡萄糖胺补充剂和O-GlcNAc酶抑制剂，显示广泛的临床前景，但仍面临转化挑战。


https://orcid.org/0000-0001-8714-2033 (Huawu Gao); 

https://orcid.org/0000-0002-7066-9901 (Wenwen Si); 

https://orcid.org/0000-0002-3375-0073 (Biao Cai)

关键词: 阿尔茨海默病, 肌萎缩侧索硬化, HBP, 亨廷顿病, 神经再生, 神经变性, 神经元功能, OGA, O-GlcNAc, OGT, 帕金森病

Abstract: Neurodegenerative disorders are typically caused by harmful protein accumulation and nerve cell damage. A post-translational modification called O-linked N-acetylglucosamine ylation acts as a critical regulator in these disorders by controlling protein behavior, cell signaling, and energy balance. This modification is dynamically balanced through the cooperative actions of O-linked N-acetylglucosamine transferase and O-GlcNAcase. In healthy brains, O-GlcNAcylation supports nerve cell function and survival, but its imbalance contributes to disease progression. Notably, the effects of O-GlcNAcylation differ across disorders. This review reveals how O-GlcNAcylation bridges molecular mechanisms to neurodegeneration, as well as the prospects of targeted O-linked N-acetylglucosamine acylation therapy for neurodegenerative diseases. In Alzheimer’s disease, it blocks toxic changes in key proteins like tau and amyloid-beta. In Parkinson’s disease, it reduces the clumping of alpha-synuclein, yet may disrupt dopamine production. In amyotrophic lateral sclerosis, it protects nerve fiber transport systems. Additionally, O-GlcNAcylation plays an indispensable part in other neurodegenerative conditions, including Huntington’s disease, aging, Machado- Joseph disease, multiple sclerosis, and giant axonal neuropathy. New therapies targeting this mechanism include glucosamine supplements and O-GlcNAcase inhibitors, which show clinical promise but face translational challenges. 

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, neural regeneration, neurodegeneration, neuronal function, O-GlcNAcase, O-linked N-acetylglucosamine, O-linked N-acetylglucosamine transferase, Parkinson’s disease