阿尔茨海默症铜和铁代谢的研究进展
Research Progress on Copper and Iron Metabolism in Alzheimer’s Disease
DOI: 10.12677/hjbm.2025.154075, PDF,    科研立项经费支持
作者: 黄沙沙, 黄丹丹, 高韵涵, 尹琳茜, 徐 微*：嘉兴南湖学院新材料工程学院，浙江 嘉兴
关键词: 阿尔茨海默症；铜代谢；铁代谢；金属离子；Alzheimer’s Disease； Copper Metabolism； Iron Metabolism； Metal Ions
摘要: 阿尔茨海默症(Alzheimer’s disease, AD)是一种复杂的神经退行性疾病，其发病机制尚未完全阐明。近年来的研究表明，体内金属离子的代谢异常，尤其是铜和铁的代谢失衡，与该病的发病密切相关。铜和铁的异常积累对淀粉样斑块的形成和氧化应激水平的增加有显著影响，从而加速阿尔茨海默症的病程发展。同时，铜和铁在细胞内存在竞争与平衡，因此调节铜和铁的代谢可能为该疾病的预防和治疗提供新的策略。本文综述了铜与铁在神经系统中的生理功能，以及二者失衡对阿尔茨海默症发病进程的影响，并结合最新研究进展，探讨了基于铜和铁代谢的AD生物标志物及可能的治疗策略，为该病的预防、诊断及治疗提供思路。
Abstract: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and its pathogenesis has not been fully elucidated. Recent studies have shown that abnormal metabolism of metal ions in the brain, particularly the imbalance of copper and iron, is closely related to the onset of the disease. Abnormal accumulation of copper and iron significantly affects the formation of amyloid plaques and increases oxidative stress levels, thereby accelerating the progression of Alzheimer’s disease. Further, there is competition and equilibrium between copper and iron within cells, so regulating their metabolism may provide new strategies for the prevention and treatment of the disease. This article reviews the physiological functions of copper and iron in the nervous system, as well as the impact of their imbalance on the progression of Alzheimer’s disease. It also discusses AD biomarkers and potential therapeutic strategies based on copper and iron metabolism, providing insights for the prevention, diagnosis, and treatment of the disease.
文章引用：黄沙沙, 黄丹丹, 高韵涵, 尹琳茜, 徐微. 阿尔茨海默症铜和铁代谢的研究进展[J]. 生物医学, 2025, 15(4): 681-687. https://doi.org/10.12677/hjbm.2025.154075

参考文献

[1] Zhang, Y., Yang, Y., Wang, C., Chen, W., Chen, X., Wu, F., et al. (2023) Copper Metabolism-Related Genes in Entorhinal Cortex for Alzheimer’s Disease. Scientific Reports, 13, Article No. 17458. [Google Scholar] [CrossRef] [PubMed]
[2] Zhang, Y., Wang, M. and Chang, W. (2022) Iron Dyshomeostasis and Ferroptosis in Alzheimer’s Disease: Molecular Mechanisms of Cell Death and Novel Therapeutic Drugs and Targets for Ad. Frontiers in Pharmacology, 13, Article ID: 983623. [Google Scholar] [CrossRef] [PubMed]
[3] Locatelli, M. and Farina, C. (2024) Role of Copper in Central Nervous System Physiology and Pathology. Neural Regeneration Research, 20, 1058-1068. [Google Scholar] [CrossRef] [PubMed]
[4] Zhong, G., Wang, X., Li, J., Xie, Z., Wu, Q., Chen, J., et al. (2024) Insights into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds. Current Neuropharmacology, 22, 1650-1671. [Google Scholar] [CrossRef] [PubMed]
[5] Wang, Y., Li, D., Xu, K., Wang, G. and Zhang, F. (2024) Copper Homeostasis and Neurodegenerative Diseases. Neural Regeneration Research, 20, 3124-3143. [Google Scholar] [CrossRef] [PubMed]
[6] Zhu, Z., Song, M., Ren, J., Liang, L., Mao, G. and Chen, M. (2024) Copper Homeostasis and Cuproptosis in Central Nervous System Diseases. Cell Death & Disease, 15, Article No. 850. [Google Scholar] [CrossRef] [PubMed]
[7] Li, Y., Han, Y., Shu, Q., Kan, Y. and Wang, Z. (2025) Cuproptosis and Copper as Potential Mechanisms and Intervention Targets in Alzheimer’s Disease. Biomedicine & Pharmacotherapy, 183, Article ID: 117814. [Google Scholar] [CrossRef] [PubMed]
[8] Sasanian, N., Bernson, D., Horvath, I., Wittung-Stafshede, P. and Esbjörner, E.K. (2020) Redox-Dependent Copper Ion Modulation of Amyloid-β (1-42) Aggregation in Vitro. Biomolecules, 10, Article No. 924. [Google Scholar] [CrossRef] [PubMed]
[9] Crnich, E., Lullo, R., Tabaka, A., Havens, M.A. and Kissel, D.S. (2021) Interactions of Copper and Copper Chelate Compounds with the Amyloid Beta Peptide: An Investigation into Electrochemistry, Reactive Oxygen Species and Peptide Aggregation. Journal of Inorganic Biochemistry, 222, Article ID: 111493. [Google Scholar] [CrossRef] [PubMed]
[10] Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C. and Collin, F. (2018) Oxidative Stress and the Amyloid Beta Peptide in Alzheimer’s Disease. Redox Biology, 14, 450-464. [Google Scholar] [CrossRef] [PubMed]
[11] Mezzanotte, M. and Stanga, S. (2024) Brain Iron Dyshomeostasis and Ferroptosis in Alzheimer’s Disease Pathophysiology: Two Faces of the Same Coin. Aging and Disease.
[12] Peng, Y., Chang, X. and Lang, M. (2021) Iron Homeostasis Disorder and Alzheimer’s Disease. International Journal of Molecular Sciences, 22, Article No. 12442. [Google Scholar] [CrossRef] [PubMed]
[13] Wang, T., Xu, S., Fan, Y., Li, L. and Guo, C. (2019) Iron Pathophysiology in Alzheimer’s Diseases. In: Chang, Y.-Z., Ed., Brain Iron Metabolism and CNS Diseases, Springer, 67-104. [Google Scholar] [CrossRef] [PubMed]
[14] Peng, W., Chung, K.B., Lawrence, B.P., O’Banion, M.K., Dirksen, R.T., Wojtovich, A.P., et al. (2024) DMT1 Knockout Abolishes Ferroptosis Induced Mitochondrial Dysfunction in C. Elegans Amyloid Β Proteotoxicity. Free Radical Biology and Medicine, 224, 785-796. [Google Scholar] [CrossRef] [PubMed]
[15] Zhuang, X., Xia, Y., Liu, Y., Guo, T., Xia, Z., Wang, Z., et al. (2024) SCG5 and MITF May Be Novel Markers of Copper Metabolism Immunorelevance in Alzheimer’s Disease. Scientific Reports, 14, Article No. 13619. [Google Scholar] [CrossRef] [PubMed]
[16] Zhang, G., Zhang, Y., Shen, Y., Wang, Y., Zhao, M. and Sun, L. (2021) The Potential Role of Ferroptosis in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 80, 907-925. [Google Scholar] [CrossRef] [PubMed]
[17] Wang, J., Fu, J., Zhao, Y., Liu, Q., Yan, X. and Su, J. (2023) Iron and Targeted Iron Therapy in Alzheimer’s Disease. International Journal of Molecular Sciences, 24, Article No. 16353. [Google Scholar] [CrossRef] [PubMed]
[18] Gromadzka, G., Wilkaniec, A., Tarnacka, B., Hadrian, K., Bendykowska, M., Przybyłkowski, A., et al. (2024) The Role of Glia in Wilson’s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives. International Journal of Molecular Sciences, 25, Article No. 7545. [Google Scholar] [CrossRef] [PubMed]
[19] Soczewka, P., Tribouillard-Tanvier, D., di Rago, J., Zoladek, T. and Kaminska, J. (2021) Targeting Copper Homeostasis Improves Functioning of Vps13δ Yeast Mutant Cells, a Model of Vps13-Related Diseases. International Journal of Molecular Sciences, 22, Article No. 2248. [Google Scholar] [CrossRef] [PubMed]
[20] Singh, R., Panghal, A., Jadhav, K., Thakur, A., Verma, R.K., Singh, C., et al. (2024) Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer’s Disease. Molecular Neurobiology, 61, 10916-10940. [Google Scholar] [CrossRef] [PubMed]
[21] Gromadzka, G., Tarnacka, B., Flaga, A. and Adamczyk, A. (2020) Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications. International Journal of Molecular Sciences, 21, Article No. 9259. [Google Scholar] [CrossRef] [PubMed]
[22] Metsla, K., Kirss, S., Laks, K., Sildnik, G., Palgi, M., Palumaa, T., et al. (2022) Α-Lipoic Acid Has the Potential to Normalize Copper Metabolism, Which Is Dysregulated in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 85, 715-728. [Google Scholar] [CrossRef] [PubMed]
[23] Cilliers, K. (2021) Trace Element Alterations in Alzheimer’s Disease: A Review. Clinical Anatomy, 34, 766-773. [Google Scholar] [CrossRef] [PubMed]
[24] Simunkova, M., Alwasel, S.H., Alhazza, I.M., Jomova, K., Kollar, V., Rusko, M., et al. (2019) Management of Oxidative Stress and Other Pathologies in Alzheimer’s Disease. Archives of Toxicology, 93, 2491-2513. [Google Scholar] [CrossRef] [PubMed]
[25] Doroszkiewicz, J., Farhan, J.A., Mroczko, J., Winkel, I., Perkowski, M. and Mroczko, B. (2023) Common and Trace Metals in Alzheimer’s and Parkinson’s Diseases. International Journal of Molecular Sciences, 24, Article No. 15721. [Google Scholar] [CrossRef] [PubMed]
[26] Wang, H., Yu, P., Guo, X., Wang, W., Wang, L., Zhang, H., et al. (2025) Mechanistic Insights for Efficient Removal of Intracellular and Extracellular Antibiotic Resistance Genes by Iron-Based Nanocopper: Intracellular Oxidative Stress and Internalization of Nanocopper. Journal of Hazardous Materials, 484, Article ID: 136745. [Google Scholar] [CrossRef] [PubMed]
[27] Du, Y., Chen, X., Zhang, B., Jin, X., Wan, Z., Zhan, M., et al. (2023) Identification of Copper Metabolism Related Biomarkers, Polygenic Prediction Model, and Potential Therapeutic Agents in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 95, 1481-1496. [Google Scholar] [CrossRef] [PubMed]
[28] Cerasuolo, M., Di Meo, I., Auriemma, M.C., Trojsi, F., Maiorino, M.I., Cirillo, M., et al. (2023) Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia. International Journal of Molecular Sciences, 24, Article No. 9637. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, B. and Burke, R. (2023) Copper Homeostasis and the Ubiquitin Proteasome System. Metallomics, 15, mfad010. [Google Scholar] [CrossRef] [PubMed]
[30] Kowalczyk, J., Grapsi, E., Espargaró, A., Caballero, A.B., Juárez-Jiménez, J., Busquets, M.A., et al. (2021) Dual Effect of Prussian Blue Nanoparticles on Aβ40 Aggregation: Β-Sheet Fibril Reduction and Copper Dyshomeostasis Regulation. Biomacromolecules, 22, 430-440. [Google Scholar] [CrossRef] [PubMed]
[31] Kawahara, M., Kato-Negishi, M. and Tanaka, K. (2023) Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases. Nutrients, 15, Article No. 2067. [Google Scholar] [CrossRef] [PubMed]

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