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 (9): 4211-4220.doi: 10.4103/NRR.NRR-D-25-00632

• 综述:退行性病与再生 • 上一篇    下一篇

锌稳态失衡：在神经退行性疾病中的潜在治疗价值


  

  • 出版日期:2026-09-15 发布日期:2026-05-19
  • 基金资助:
    国家自然科学基金（82360162；82160371）、江西省科学技术协会青年精英科学家资助计划（2023QT05）、江西省自然科学基金（20224ACB216009；202201011395）、江西省自然科学基金（20224ACB216009； 202201011395，20224ACB216009）；广东省自然科学基金项目（202201011395）；江西省千人计划项目（jxsq2023201105）；恒瑞糖尿病代谢研究基金（Z-2017-26-2202-4）

Zinc homeostasis imbalance: Potential therapeutic value in neurodegenerative diseases

Zheyi Zhang1, Wei Deng2, 3, Leilai Hu3, Yulong Hu3, Shenglan Zhang3, Yaping Xiong3, Xiao Liu4, Peng Yu5, Shuchun Yu3, Linhui Yuan3, *, Jing Zhang3, *   

  1. 1The Second Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; 
    2Department of Anesthesiology, Jiujiang University Affiliated Hospital, Jiujiang, Jiangxi Province, China; 
    3Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; 
    4Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China; 
    5Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • Online:2026-09-15 Published:2026-05-19
  • Contact: Linhui Yuan, PhD, 631973877@qq.com; Jing Zhang, PhD, ndefy01467@ncu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82360162 (to PY), 82160371 (to JZ); Young Elite Scientists Sponsorship Program by Jiangxi Association for Science and Technology, No. 2023QT05 (to JZ); the Natural Science Foundation of Jiangxi Province, No. 20224ACB216009 (to JZ); the Natural Science Foundation of Guangdong Province, No. 202201011395 (to XL); the Jiangxi Province Thousands Project Plan, No. jxsq2023201105 (to PY); and the Hengrui Diabetes Metabolism Research Fund, No. Z-2017-26-2202-4 (to PY).

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摘要：

锌稳态基因是调控细胞内外锌离子浓度基因家族的统称，包括SLC39（ZIP）家族、SLC30（ZnT）家族及金属硫蛋白家族。作为必需微量元素，锌参与生物分子合成、能量代谢、氧化还原调节及基因表达。近期研究表明，锌稳态基因异常表达通过氧化应激、神经炎症等途径介导神经元凋亡。锌稳态失衡参与多种神经退行性疾病的病理发展，包括阿尔茨海默病中β淀粉样蛋白的沉积，以及帕金森病中α-突触核蛋白的异常聚集。因此，靶向调控锌稳态基因表达以恢复体内正常锌水平，可能是治疗神经退行性疾病的有效策略。文章的目的是综述多学科领域对不同家族亚型锌稳态基因的研究现状，以及各类神经退行性疾病中锌稳态基因表达改变及其潜在机制。使用锌螯合剂调节锌稳态基因表达可逆转该过程，文章最后重点提出了将锌螯合剂补充疗法作为神经退行性疾病的新型干预手段的可行性、安全性及局限性，为未来神经退行性疾病的临床治疗提供了创新性视角。


http://orcid.org/0009-0004-0635-6072 (Linhui Yuan)

关键词: 阿尔茨海默病, 神经炎症, 神经元细胞死亡, 氧化应激, 帕金森病, 精神分裂症, 突触功能障碍, 锌稳态基因, 锌信号通路, 锌螯合剂

Abstract: Zinc homeostasis genes are a general term for a family of genes responsible for regulating the concentration of intracellular and extracellular zinc ions, including the SLC39 (ZIP) family, the SLC30 (ZnT) family, and the metallothionein family. As an essential trace element, zinc is involved in biomolecular synthesis, energy metabolism, redox regulation, and gene expression. Recent studies have shown that abnormal expression of zinc homeostasis genes mediates neuronal apoptosis through multiple pathways, including oxidative stress and neuroinflammation. Imbalance in zinc homeostasis can result in the pathological development of various neurodegenerative disorders, including the deposition of amyloid-β in Alzheimer’s disease and the aberrant aggregation of α-synuclein in Parkinson’s disease. Therefore, regulating the expression of zinc homeostasis genes to restore normal zinc levels in vivo may be an effective strategy for treating neurodegenerative diseases. This review comprehensively summarizes the current status of research exploring zinc homeostasis genes across various family subtypes, as well as the altered expression of these genes in different neurodegenerative diseases and the underlying mechanisms. Finally, we propose zinc chelator supplementation as a novel interventional therapy for neurodegenerative diseases. This proposal includes an evaluation of the feasibility, safety, and limitations of this treatment, providing an innovative perspective for the clinical management of neurodegenerative diseases in the future. 

Key words: Alzheimer’s disease, neuroinflammation, neuronal cell death, oxidative stress, Parkinson’s disease, Schizophrenia, synaptic dysfunction, zinc chelators, zinc homeostasis genes, zinc signaling pathways