Copper homeostasis and cuproptosis in central nervous system diseases DOI Creative Commons
Zhipeng Zhu, Min Song,

Jianxun Ren

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(11)

Published: Nov. 20, 2024

Abstract Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array fundamental metabolic processes. The human body maintains relatively low concentration copper, which is mostly found in bones, liver, and brain. Despite its concentration, Cu plays crucial role as element progression pathogenesis central nervous system (CNS) diseases. Extensive studies have been conducted recent years on copper homeostasis copper-induced cell death CNS disorders, including glioma, Alzheimer’s disease, Amyotrophic lateral sclerosis, Huntington’s stroke. Cuproptosis, novel pathway distinct from apoptosis, necrosis, pyroptosis, ferroptosis, has identified potentially intricately linked pathogenic mechanisms underlying various Therefore, systematic review cuproptosis their relationship with disorders could deepen our understanding these In addition, it may provide new insights strategies treatment disorders.

Language: Английский

Cuproptosis: Harnessing Transition Metal for Cancer Therapy DOI
Wuyin Wang, Wentao Mo, Zishan Hang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Language: Английский

Citations

82
FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery DOI Creative Commons
Mohammad Zulkifli,

Amy N. Spelbring,

Yuteng Zhang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(10)

Published: Feb. 27, 2023

Recent studies have uncovered the therapeutic potential of elesclomol (ES), a copper-ionophore, for copper deficiency disorders. However, we currently do not understand mechanism by which brought into cells as ES–Cu(II) is released and delivered to cuproenzymes present in different subcellular compartments. Here, utilized combination genetic, biochemical, cell-biological approaches demonstrate that intracellular release from ES occurs inside outside mitochondria. The mitochondrial matrix reductase, FDX1, catalyzes reduction Cu(I), releasing it mitochondria where bioavailable metalation cuproenzyme— cytochrome c oxidase. Consistently, fails rescue oxidase abundance activity copper-deficient lacking FDX1. In absence ES-dependent increase cellular attenuated but abolished. Thus, ES-mediated delivery nonmitochondrial cuproproteins continues even suggesting alternate mechanism(s) release. Importantly, this transport distinct other clinically used copper-transporting drugs. Our study uncovers unique mode may further aid repurposing anticancer drug

Language: Английский

Citations

63
Oxygen‐driven cuproptosis synergizes with radiotherapy to potentiate tumor immunotherapy DOI Creative Commons
Pei Pei,

Yuhong Wang,

Wenhao Shen

et al.

Aggregate, Journal Year: 2024, Volume and Issue: 5(3)

Published: Jan. 4, 2024

Abstract The immunological implications of cuproptosis, a form cell death highly sensitive to oxygen presence, remain largely unexplored in the context tumor immunotherapy. Herein, we initially investigate positive correlation between cuproptosis and immunotherapy through bioinformatics analysis. Subsequently, an generator loaded with copper ions ( Cu/AP H‐M) has been constructed, which serves as effective carrier crucially enhances oxygenation microenvironment. Importantly, H‐M‐mediated dual strengthening radiotherapy could not only trigger powerful antitumor immunity related immunogenic by RNA‐sequencing analysis, but also effectively inhibit growth both distal situ low rectal tumors after combined immunotherapy, creating robust immune memory effect. Our work reveals beneficial effects enhanced radio‐immunotherapy elucidates its underlying mechanisms, provides novel approach for synergistic integration radiotherapy, broadening scope cuproptosis‐mediated therapy.

Language: Английский

Citations

29
Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes DOI Creative Commons
Na Chen, Lizhe Guo, Lu Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 7, 2024

Abstract Sleep disorders increase the risk and mortality of heart disease, but brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type cell death activated by excessive accumulation intracellular copper. Here, we showed that 16 weeks sleep fragmentation (SF) resulted in elevated copper levels male mouse exacerbated myocardial ischemia–reperfusion injury with increased cuproptosis apoptosis. Mechanistically, found SF promotes sympathetic overactivity, increases germination nerve terminals, level norepinephrine cardiac tissue, thereby inhibits VPS35 expression leads to impaired ATP7A related transport overload cardiomyocytes. Copper further apoptosis, these effects can be rescued excision or administration chelating agent. Our study elucidates one molecular mechanisms which aggravate suggests possible targets for intervention.

Language: Английский

Citations

22
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives DOI Creative Commons
Chenliang Zhang, Tingting Huang, Liping Li

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Language: Английский

Citations

18
Dissecting copper biology and cancer treatment: ‘Activating Cuproptosis or suppressing Cuproplasia’ DOI
Ying Yang, Man Li, Gang Chen

et al.

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 495, P. 215395 - 215395

Published: Aug. 22, 2023

Language: Английский

Citations

40
Emerging roles of MITF as a crucial regulator of immunity DOI Creative Commons
Aram Lee, Ji‐Hyun Lim, Jong‐Seok Lim

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(2), P. 311 - 318

Published: Feb. 13, 2024

Abstract Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper (bHLH-Zip), has been identified as melanocyte-specific and plays critical role in melanocyte survival, differentiation, function, proliferation pigmentation. Although numerous studies have explained the roles of MITF melanocytes melanoma development, function hematopoietic or immune system—beyond its melanin-producing cells—is not yet fully understood. However, there is convincing increasing evidence suggesting that may play multiple important immune-related cells. Therefore, this review focused on recent advances elucidating novel functions cancer progression responses to cancer. In particular, we highlight central modulator regulation responses, elucidated studies.

Language: Английский

Citations

12
Protein lipoylation: mitochondria, cuproptosis, and beyond DOI
Cheng-Han Lin, Yeh Chin, Ming Zhou

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(8), P. 729 - 744

Published: May 6, 2024

Language: Английский

Citations

12
Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases DOI
Zhibo Yang,

Ridong Feng,

Zhao Hai

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(9-10), P. 1330 - 1360

Published: July 16, 2024

Language: Английский

Citations

12
The crosstalk between mitochondrial quality control and metal-dependent cell death DOI Creative Commons

Qi-yuan Zhou,

Chao Ren,

Jing‐Yan Li

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 27, 2024

Abstract Mitochondria are the centers of energy and material metabolism, they also serve as storage dispatch hubs metal ions. Damage to mitochondrial structure function can cause abnormal levels distribution ions, leading cell dysfunction even death. For a long time, quality control pathways such dynamics mitophagy have been considered inhibit metal-induced However, with discovery new metal-dependent death including ferroptosis cuproptosis, increasing evidence shows that there is complex relationship between This article reviews latest research results mechanisms crosstalk in recent years, well their involvement neurodegenerative diseases, tumors other order provide ideas for treatment related diseases.

Language: Английский

Citations

11