Genchi Giuseppe, Catalano Alessia, Carocci Alessia, Sinicropi Maria Stefania, Lauria Graziantonio
Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro", 70126 Bari, Italy.
Int J Mol Sci. 2025 Sep 19;26(18):9173. doi: 10.3390/ijms26189173.
Copper is a vital micronutrient for animals and plants acting as a crucial cofactor in the synthesis of numerous metabolic enzymes and contributing to mitochondrial respiration, metabolism, oxido-reductive reactions, signal transmission, and oxidative and nitrosative damage. In the cells, copper may exist in the Cu and Cu oxidation states and the interconversion between these two states may occur via various redox reactions regulating cellular respiration, energy metabolism, and cell growth. The human body maintains a low level of copper, and copper deficiency or copper excess may adversely affect cellular functions; therefore, regulation of copper levels within a narrow range is important for maintaining metabolic homeostasis. Recent studies identified a new copper-dependent form of cell death called cuproptosis. Cuproptosis occurs due to copper binding to lipoylated enzymes (for instance, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the tricarboxylic acid Krebs cycle. In recent years, extensive studies on copper homeostasis and copper-induced cell death in degenerative disorders, like Menkes, Wilson, Alzheimer, Parkinson's, Huntington's diseases, and Amyotrophic Lateral Sclerosis, have discussed the therapeutic potential of targeting cuproptosis. Copper contamination in the environment, which has increased in recent years due to the expansion of agricultural and industrial activities, is associated with a wide range of human health risks. Soil used for the cultivation of grapes has a long history of copper-based fungicide application (the Bordeaux mixture is rich in copper) resulting in copper accumulation at levels capable of causing toxicity in plants that co-inhabit the vineyards. Phytoremediation, which uses plants and biological solutions to remove toxic heavy metals and pesticides and other contaminants from soil and water, is an environmentally friendly and cost-effective technology used for the removal of copper. It requires plants to be tolerant of high levels of copper and capable of accumulating metal copper in plants' aerial organs and roots. This review aims at highlighting the importance of copper as an essential metal, as well as its involvement in cuproptosis and neurodegenerative diseases.
铜是动植物必需的微量营养素，在众多代谢酶的合成中作为关键辅助因子，参与线粒体呼吸、新陈代谢、氧化还原反应、信号传导以及氧化和亚硝化损伤过程。在细胞中，铜可能以Cu⁺和Cu²⁺氧化态存在，这两种状态之间的相互转化可通过各种调节细胞呼吸、能量代谢和细胞生长的氧化还原反应发生。人体维持着较低水平的铜，铜缺乏或过量都可能对细胞功能产生不利影响；因此，将铜水平调节在狭窄范围内对于维持代谢稳态很重要。最近的研究发现了一种新的依赖铜的细胞死亡形式，称为铜死亡。铜死亡是由于铜与三羧酸循环中的硫辛酸化酶（如丙酮酸脱氢酶和α-酮戊二酸脱氢酶）结合而发生的。近年来，在诸如门克斯病、威尔逊病、阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症等退行性疾病中，对铜稳态和铜诱导的细胞死亡进行了广泛研究，探讨了靶向铜死亡的治疗潜力。由于农业和工业活动的扩张，近年来环境中的铜污染有所增加，这与广泛的人类健康风险相关。用于种植葡萄的土壤长期使用含铜杀菌剂（波尔多液富含铜），导致铜积累到能够对同处葡萄园的植物产生毒性的水平。植物修复利用植物和生物溶液从土壤和水中去除有毒重金属、农药和其他污染物，是一种用于去除铜的环保且经济高效的技术。它要求植物耐受高水平的铜，并能够在植物地上器官和根部积累金属铜。本综述旨在强调铜作为必需金属的重要性，以及它在铜死亡和神经退行性疾病中的作用。
