Biometals最新文献

{"title":"Genome-based identification of heavy metal resistance-associated genes in Bacillus enclensis ABF750 isolated from the polluted sediment of Versova Creek","authors":"Abhay B. Fulke,&nbsp;Nilkanth Sharma,&nbsp;Swati Sonker,&nbsp;Jayshree S. Nadekar","doi":"10.1007/s10534-026-00845-3","DOIUrl":"10.1007/s10534-026-00845-3","url":null,"abstract":"<div><p>Heavy metal pollution is a major environmental concern in coastal ecosystems, particularly in urban estuarine systems where anthropogenic activities lead to the accumulation of toxic metals in sediments and water bodies. The urgent need to identify microorganisms capable of tolerating and remediating heavy metal contamination has driven interest in environmentally adapted bacterial strains. In the present study, a bacterial strain, <i>Bacillus enclensis</i> ABF750, was isolated from sediment collected from the highly polluted Versova Creek, Mumbai, India, and its adaptive potential was investigated using whole-genome phylogenetic analysis and functional genome annotation. Genomic analysis revealed the presence of numerous heavy metal resistance determinants, including genes involved in metal sensing, detoxification, transport, and efflux mechanisms, along with siderophore-associated biosynthetic pathways that contribute to metal chelation and stress tolerance. Sediment analysis confirmed multi-metal contamination, while water quality measurements indicated extreme environmental conditions characterized by persistent anoxia (0 mg/L dissolved oxygen), high biological oxygen demand (28.51–41.18 mg/L), and elevated ammonium (186.74–243.3 µmol/L) and phosphate (25.4–29.63 µmol/L) concentrations. These physicochemical conditions demonstrate the highly stressed nature of the habitat and highlight the remarkable adaptability of <i>B. enclensis</i> ABF750 to nutrient toxicity, salinity fluctuations, and metal stress. Collectively, these findings demonstrate that Versova Creek represents a severely stressed and anthropogenically impacted estuarine habitat characterized by persistent anoxia, nutrient enrichment, and multi-metal contamination with promising potential for bioremediation of metal-contaminated coastal ecosystems.</p><h3>Graphic abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"1995 - 2013"},"PeriodicalIF":4.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and biological evaluation of a histidine-bearing cyclometalated Pd(II) complex derived from 2-phenylpyridine","authors":"Sedigheh Abedanzadeh","doi":"10.1007/s10534-026-00849-z","DOIUrl":"10.1007/s10534-026-00849-z","url":null,"abstract":"<div><p>A rationally designed approach was employed to synthesize a new C^N-cyclometalated Pd(II) complex (C^N = 2-phenylpyridine) as a potential anticancer metallodrug. The incorporation of histidine in the coordination sphere of metal complex offers dual effect, balancing hydrophobic and hydrophilic properties while enhancing biocompatibility. The structure of histidine-bearing C^N-cyclometalated Pd(II) complex was characterized using elemental analysis, FT-IR, and NMR spectroscopy. In vitro cytotoxic activity was evaluated against HEP G2 human hepatoma and MCF7 human breast cancer cells revealing high selectivity of complex toward HEP G2 compared to MCF7 cancer cells. The effect of complex on NIH-3T3 mouse embryonic fibroblast normal cells were also assessed. To elucidate the mechanism of action, binding interactions with DNA were investigated using UV–Vis and fluorescence spectroscopy demonstrating preferential binding to the minor groove of DNA, suggesting a DNA-targeting mechanism. Additionally, the complex exhibited strong affinity for bovine serum albumin (BSA) with through a static quenching process. These findings suggest that the integration of amino acids into the coordination sphere of cyclometalated complexes can address the limitations of traditional metal-based anticancer agents by improving drug stability and biocompatibility.</p><h3>Graphical Abstract</h3><p>The present work provides an experimental investigation for the DNA and BSA binding interactions of a newly synthesized cyclometalated Pd (II) complex bearing histidine as a biologically active, biocompatible coordinating ligand which can be further studied as a potential metal-based antitumor agent.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"2047 - 2060"},"PeriodicalIF":4.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between metal co-exposure and frailty: exploring the potential explanatory pathway of inflammation","authors":"Dongmei Yu,&nbsp;Yue Wei,&nbsp;Yan-Feng Zhou,&nbsp;Junxiu He,&nbsp;Yu Bao,&nbsp;Lun Liang,&nbsp;Dongyi Feng,&nbsp;Yujin Li,&nbsp;Hong Cheng,&nbsp;Haiqing Cai,&nbsp;Xing Chen,&nbsp;Xiaobo Yang","doi":"10.1007/s10534-026-00853-3","DOIUrl":"10.1007/s10534-026-00853-3","url":null,"abstract":"<div><p>Frailty is a critical geriatric syndrome associated with disability and mortality, yet the associations and mechanisms between environmental metal co-exposure with frailty remain unclear. This cross-sectional study included 4484 adults aged ≥ 60 years from China. Metal concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and frailty was assessed using a frailty index (FI). Single-metal analyses used generalized linear models (GLMs). For multi-metal analyses, we applied machine-learning-based variable selection, followed by Bayesian kernel machine regression (BKMR) and quantile g-computation (qg-comp) model. Potential explanatory pathways involving inflammatory markers, as well as interactions with age, sex, and lifestyle, were also explored. Positive associations were observed for magnesium (Mg), molybdenum (Mo), and vanadium (V) with FI, whereas rubidium (Rb) showed an inverse association (<i>P</i> &lt; 0.001). Significant effect modification by age, sex, and lifestyle was identified. Positive metal‑FI associations were stronger in older females, while the inverse Rb‑FI correlation was more evident in participants with unhealthy lifestyles (<i>P</i> for interaction &lt; 0.05). Multi-metal models showed overall positive co-exposure effects on frailty, with Mo (positive) and Rb (negative) contributing the largest weights. In exploratory mediation analyses, the neutrophil-to-high-density lipoprotein ratio (NHR) accounted for 2.09% of the Rb–FI association and 1.81% of the Mo–FI association. The platelet-to-albumin ratio (PAR) accounted for 1.52% of the Mo–FI association and 5.30% of the Mg–FI association (<i>P</i> &lt; 0.05). These findings suggest that metal co-exposure is positively associated with frailty, with inflammation as a potential explanatory pathway. Metal‑frailty associations vary by age, sex and lifestyle, with distinct patterns for different metals. Although longitudinal studies are needed to establish temporality and causal pathways, these findings identify high-risk subgroups for future investigation.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"2105 - 2121"},"PeriodicalIF":4.0,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of aluminum absorption in Caenorhabditis elegans: pre-treatment optimization and the impact of dose and population size","authors":"Dilara Ülger Özbek,&nbsp;Yoncagül Nar,&nbsp;Şeyda Berk,&nbsp;Özgür Ülkü Özdemir","doi":"10.1007/s10534-026-00854-2","DOIUrl":"10.1007/s10534-026-00854-2","url":null,"abstract":"<div><p>Accurate quantification of aluminum (Al) uptake is essential for evaluating metal toxicity in experimental models. This study aimed to optimize pretreatment strategies and determine the effects of individual number and dose on Al accumulation and assess the biological relevance of Al exposure in the <i>Caenorhabditis elegans</i> model. The investigation was conducted in two stages. In the first stage, synchronized groups of 10, 25, 50, 100, 200, and 400 worms, along with controls, were exposed to 10, 15, and 25 mM AlCl₃ for seven days After exposure, worms were washed to remove Al from the culture medium, viability was terminated using nitric acid, and Al levels were quantified by ICP-MS without pretreatment. In the second stage, 50 worms exposed to 100 mM AlCl₃ for seven days and subjected to four different pretreatment protocols prior to ICP-MS analysis. Reproductive toxicity was additionally evaluated to determine the biological impact of Al accumulation. Significant dose-dependent increases in Al uptake were observed, particularly in groups containing 10, 25, and 50 worms (first trial). Among pretreatment methods (second trials), the combined sonication and centrifugation supernatant protocol yielded the highest Al levels (78.47 mM), followed by pretreatment A (68.68 mM), C (64.52 mM), and B (59.60 mM). Furthermore, Al exposure significantly reduced reproductive capacity compared with controls These findings demonstrate that both organism number and pretreatment strategy critically influence Al quantification and confirm that accumulated Al is associated with biologically relevant toxic effects. The optimized methodology provides a robust framework for future metal toxicity studies.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"2123 - 2133"},"PeriodicalIF":4.0,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in therapeutic agents for uranium poisoning: a comprehensive review","authors":"Juan Li,&nbsp;Wenrun Li,&nbsp;Feng Huang,&nbsp;Qiuchi Wang,&nbsp;Hongjia Liu,&nbsp;Liyi Chen,&nbsp;Qiuping Wang,&nbsp;Yong Li,&nbsp;Shiyan Fu,&nbsp;Yazhen Zhao,&nbsp;Yonghong Ran,&nbsp;Yuhui Hao","doi":"10.1007/s10534-026-00848-0","DOIUrl":"10.1007/s10534-026-00848-0","url":null,"abstract":"<div><p>Uranium—an emerging pollutant that exhibits both radioactivity and heavy metal toxicity—is extensively used in nuclear fuel and military applications. Occupational and environmental exposure during its extraction, production, and utilization poses significant health risks. Consequently, developing effective countermeasures against uranium poisoning remains a critical challenge in the field of medical research. This review systematically introduces the latest experimental progress in research on drugs for treating uranium toxicity. It specifically elucidates the mechanisms and efficacy evaluations of multiple detoxification strategies, including chelating agents, nanomedicines, biosynthetic compounds, small molecules, natural medicines, and plant extracts. By analyzing innovative drug design principles and evaluating their mechanistic effects on uranium toxicity, this work provides critical insights for the future development of highly effective and low-toxicity novel therapies for uranium poisoning.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"1399 - 1420"},"PeriodicalIF":4.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioaccessibility of metals in food supplements: protocols and facts","authors":"Thaís dos Santos Berón,&nbsp;Gustavo Rossato Bitencourt,&nbsp;Rochele Sogari Picoloto,&nbsp;Rodrigo Cordeiro Bolzan,&nbsp;Paola Azevedo Mello","doi":"10.1007/s10534-026-00844-4","DOIUrl":"10.1007/s10534-026-00844-4","url":null,"abstract":"<div><p>This study evaluated the bioaccessibility of essential (Ca, Cu, Fe, K, Mg, Mn, Mo, Na and Zn) and non-essential (Al, Ba, Cr, Sr and V) elements in food supplements (vitamins and/or minerals and botanicals). Extraction using in-vitro methods (Unified BARGE Method—UBM and INFOGEST) was evaluated allowing a comparison of protocols and using inductively coupled plasma optical emission spectrometry (ICP OES). Bioaccessibility values revealed differences among the elements in different types of food supplements. The limits of quantification (LOQs) obtained for some elements were relatively high for both methods due to the composition of the digests, which drastically impaired bioaccessibility assessment. As a result, most elements presented fractions lower than the LOQ, regardless of the sample. This is an important limitation promoted by interferences when analyzing these extracts by ICP-based techniques. A simple extraction using 1 mol L⁻¹ HCl was evaluated, considering that HCl is present in the solutions used in both protocols. Leaching was observed for the same elements using only the HCl solution.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"1957 - 1968"},"PeriodicalIF":4.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-026-00844-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chelation treatment in a novel sub-toxic multi-metal model in rats","authors":"Janna Markov,&nbsp;Zohar Shpilt Mayer,&nbsp;Adi Ticher,&nbsp;Bracha Y. Zirkind,&nbsp;Steven Bell,&nbsp;Patricia A. J. Muller,&nbsp;Dan Gelvan","doi":"10.1007/s10534-026-00843-5","DOIUrl":"10.1007/s10534-026-00843-5","url":null,"abstract":"<div><p>Chronic, sub-toxic, multi-metal accumulation stemming from environmental exposure in daily life is a common phenomenon in modern humans and has been linked to numerous diseases. Toxic metals found in leukemia patients have recently been linked to chemoresistance and poor survival. To reverse chemoresistance, depletion of metal ions by chelators has been suggested as a possible adjuvant to chemotherapy. However, existing animal models for metal accumulation are largely unsuitable for this type of cancer research. We developed a novel accelerated model for chronic, sub-toxic, multi-metal accumulation in rats, in which a mixture of 11 metals was administered orally, followed by an equilibration period of at least five weeks to allow the metal ions to settle into their target organs in a chronic-like distribution, without overt toxicity. The model was characterized in terms of metal ion levels in urine, feces, serum, and organs. We surveyed seven chelators with different properties, seeking a compound that would specifically remove highly toxic metals, while exerting a minimal effect on essential elements. Our studies pointed to Monoisoamyl-dimercaptosuccinic acid (MiADMSA), an exploratory chelator with promising properties, as the most suitable for this purpose. Different treatment regimens, aimed at optimizing the clinical application of the chelator, were explored and characterized. Repeated monthly cycles of 5 treatments per cycle led to efficient removal of inorganic arsenic, cadmium, vanadium, and cobalt from rat organs. Our study shows that MiADMSA is a promising chelator that may be efficient in treating chronic metal accumulation, and potentially as an adjuvant to chemotherapy.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"1969 - 1994"},"PeriodicalIF":4.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative physiological and metabolomic study of Hirschfeldia incana under short- and medium-term lead (Pb) stress","authors":"Oumaima El Khattabi,&nbsp;Abdelaziz Smouni,&nbsp;Pierre Pétriacq,&nbsp;Said El Hasnaoui,&nbsp;Josep Valls,&nbsp;Clement Levard,&nbsp;Blanche Collin,&nbsp;Mouna Fahr","doi":"10.1007/s10534-026-00846-2","DOIUrl":"10.1007/s10534-026-00846-2","url":null,"abstract":"<div><p>Physiological and metabolic responses of the Pb-tolerant <i>Brassicaceae Hirschfeldia incana</i> to short-term (3 days) and medium-term (15 days) Pb exposure were evaluated. Physiological traits revealed an early and sustained control of oxidative stress. By day 3, non-enzymatic antioxidants and soluble sugars increased to support ROS quenching and promote osmotic adjustment. By day 15, POD activity further increased, while phenolic and soluble sugar contents remained elevated and chl <i>b</i> decreased selectively. Non-targeted metabolomics revealed a stronger response in roots than in shoots, highlighting the organ-specific nature of Pb tolerance in <i>H. incana</i>. Constitutive metabolic features were distinguished from time-dependent induced ones. Roots displayed a constitutive antioxidant defense driven by metabolic diversion from tryptophan and glucosinolates. Over time, this constitutive strategy was strengthened by an expansion of phenolics, particularly ferulic acid and sinapic acid to enhanced cell wall lignification. By day 15, the marked depletion of soluble non-enzymatic antioxidants (ascorbate and glutathione) likely reflected the sustained ROS turnover under elevated H₂O₂ levels. Although shoots accumulated less Pb, they still mounted an antioxidant response centered on anthocyanins and phenolics, along with an increase in small dipeptides, consistent with peptide-mediated nitrogen shuttling and repair. These data provide a comprehensive insight into the overall Pb stress response mechanisms in <i>H. incana</i>. These findings also support the potential use of this species as a model for understanding Pb tolerance and for developing phytoremediation-oriented strategies in contaminated environments.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"2015 - 2046"},"PeriodicalIF":4.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugates of desferrioxamine with 5-aminolevulinic or γ-aminobutyric acid: synthesis, theoretical studies, iron-chelating ability, and penetration in human Caco-2 cells","authors":"Ernani Lacerda,&nbsp;Vasilii D. Khripun,&nbsp;M. Teresa Machini,&nbsp;Breno Pannia Espósito","doi":"10.1007/s10534-026-00841-7","DOIUrl":"10.1007/s10534-026-00841-7","url":null,"abstract":"<div><p>Iron overload (IO) is a harmful condition in humans that promotes oxidative damage to DNA and lipids. As IO has been associated with the onset of neurodegenerative diseases (NDs), chelation therapy has been extensively used for treating IO and considered potentially suitable for NDs treatment. Desferrioxamine (DFO) presents high affinity and selectivity for iron(III), however, its clinical use as chelator is limited due to its low cell permeability. To circumvent this limitation, synthetic routes and conditions were selected for conjugating DFO to 5-aminolevulinic acid (5-ALA) or γ-aminobutyric acid (GABA), non-proteinogenic amino acids previously reported as permeable to the blood–brain barrier (BBB). Once obtained and purified, the conjugates 5-ALA-DFO and GABA-DFO were characterized by LC/ESI–MS and ¹H and ¹³C NMR. Both exhibited iron binding abilities comparable to that of DFO, displayed identical antioxidant activity, weak interactions with human serum albumin, and were unable to remove iron from transferrin (Tf). Based on DFT calculations, a theoretical model was developed that allows to predict the efficiency of iron chelation with DFO and its conjugates, in good agreement with experimental results. In assays with human colorectal adenocarcinoma (Caco-2) cells, a model for the blood–brain barrier (BBB), both chelators were non-toxic, and unlike DFO or 5-ALA-DFO, GABA-DFO was able to bind intracellular iron. Altogether, these results demonstrate that the chemical conjugation proposed here was highly effective and that GABA-DFO is a promising intracellular iron chelator.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"1921 - 1937"},"PeriodicalIF":4.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-026-00841-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the pathogenesis and therapeutic strategies of Alzheimer’s disease through cuproptosis","authors":"Shuangfeng Xu,&nbsp;Jing Mu,&nbsp;Zhifeng Wang,&nbsp;Jiao Yang,&nbsp;Daman Tian,&nbsp;Ting Shi,&nbsp;Junfeng Lan,&nbsp;Pengfen He,&nbsp;Zhihui Hao,&nbsp;Youchuan Fu,&nbsp;Liwei Xing,&nbsp;Jianzhou Ye,&nbsp;Jian Wang","doi":"10.1007/s10534-026-00835-5","DOIUrl":"10.1007/s10534-026-00835-5","url":null,"abstract":"<div><p>Alzheimer’s disease (AD), a leading cause of dementia, remains incurable, necessitating novel insights into its pathogenesis and therapeutic strategies. Recent studies highlight cuproptosis—a copper (Cu)-dependent mitochondrial cell death pathway—as a critical player in AD progression. Cuproptosis is triggered by Cu overload, which disrupts mitochondrial tricarboxylic acid cycle enzymes, resulting in toxic aggregation of lipoylated proteins and iron-sulfur cluster destabilization. This process exacerbates mitochondrial dysfunction, oxidative stress, and neuronal loss, synergizing with hallmark AD pathologies like Aβ deposition and Tau hyperphosphorylation. Unlike ferroptosis or apoptosis, cuproptosis uniquely involves mitochondrial protein lipoylation and Cu homeostasis imbalance. Therapeutic strategies targeting cuproptosis include Cu chelators, inhibitors of Cu transporters, antioxidants, and gene editing approaches to restore Cu homeostasis or mitigate protein aggregation. Immunotherapy and neuroprotective agents further show promise in alleviating cuproptosis-driven neuroinflammation. Despite preclinical advancements, challenges remain in balancing Cu’s essential roles with therapeutic interventions. This review underscores cuproptosis as a pivotal mechanism in AD and outlines emerging therapeutic avenues, emphasizing the ncessity for precision in targeting Cu dysregulation to halt neurodegeneration.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 5","pages":"1361 - 1384"},"PeriodicalIF":4.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}