Copper homeostasis and cuproptosis in cardiovascular disease therapeutics

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(9), P. 573 - 585

Published: July 25, 2023

Language: Английский

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Copper homeostasis and cuproptosis in atherosclerosis: metabolism, mechanisms and potential therapeutic strategies

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 13, 2024

Abstract Copper is an essential micronutrient that plays a pivotal role in numerous physiological processes virtually all cell types. Nevertheless, the dysregulation of copper homeostasis, whether towards excess or deficiency, can lead to pathological alterations, such as atherosclerosis. With advent concept copper-induced death, termed cuproptosis, researchers have increasingly focused on potential dyshomeostasis In this review, we provide broad overview cellular and systemic metabolism. We then summarize evidence linking atherosclerosis elucidate mechanisms underlying development terms both deficiency. Furthermore, discuss for its interactions with other modes highlight cuproptosis-related mitochondrial dysfunction Finally, explore therapeutic strategy targeting novel form aiming some insights management

Language: Английский

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Design of Near Infrared Light‐Powered Copper Phyllosilicate Nanomotors for Cuproptosis‐Based Synergistic Cancer Therapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(18)

Published: Jan. 23, 2024

Abstract Cuproptosis, a newly discovered cell death pathway, has shown great potential in cancer treatment. Herein, near‐infrared (NIR) light‐driven nanomotors (CuSiO 3 @Au‐Pd NMs) are designed for cuproptosis‐assisted synergistic therapy with autonomous mobility and improved cellular uptake tumor penetration. Specifically, the released Cu 2+ ions from CuSiO NMs can induce Fenton‐like reaction, leading to generation of hydroxyl radicals (·OH), accompanied by depletion glutathione within MCF‐7 cells. Additionally, also exhibit excellent photothermal effects, which further promote production ·OH, resulting intensified oxidative stress apoptosis. Moreover, enhanced permeation efficiency via movement under self‐thermophoretic forces proved using 2D experiments 3D multicellular spheroids. The resultant intracellular accumulation oligomerization lipoylated proteins, cuproptosis, along mitochondrial dysfunction pathway. More importantly, both vitro vivo show that could penetrate deeply into tumors anticancer efficacy through multimodal therapeutic methods. These findings manifest promising potentials NIR‐powered Cu‐based high maneuverability future smart therapy.

Language: Английский

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Alkyne-tagged SERS nanoprobe for understanding Cu+ and Cu2+ conversion in cuproptosis processes

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

Published: April 15, 2024

Abstract Simultaneously quantifying mitochondrial Cu + and 2+ levels is crucial for evaluating the molecular mechanisms of copper accumulation-involved pathological processes. Here, a series molecules containing various diacetylene derivatives as Raman reporters are designed synthesized, alkyne-tagged SERS probe created determination with high selectivity sensitivity. The developed generates well-separated distinguishable fingerprint peaks built-in corrections in cellular silent region, resulting accurate quantification . present demonstrates tempo-spatial resolution real-time imaging simultaneously long-term stability benefiting from assembly Au-C≡C groups. Using this powerful tool, it found that increase during ischemia associated breakdown proteins well conversion Meanwhile, we observe parts transported out neurons by ATPase. More importantly, cuproptosis including oxidative stress process caused to , which dominates at early stage (<9 h), subsequent proteotoxic stress. Both stresses contribute neuronal death.

Language: Английский

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Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 22, 2025

Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms signaling pathways. In this review, we delve into the cellular metabolic pathways copper, highlighting role copper biomolecule synthesis, mitochondrial respiration, antioxidant defense. Furthermore, elucidate relationship between cuproptosis-related genes (CRGs) cancer prognosis, analyzing their expression patterns across various tumor types impact on patient outcomes. Our review also uncovers potential therapeutic applications chelators, ionophores, copper-based nanomaterials oncology. addition, discuss emerging cuproptosis remodeling microenvironment, enhancing immune infiltration, converting "cold tumors" "hot that respond better to immunotherapy. short, underscores pivotal importance biology highlights translational a novel target.

Language: Английский

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Cuproptosis and copper as potential mechanisms and intervention targets in Alzheimer's disease

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117814 - 117814

Published: Jan. 13, 2025

Language: Английский

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Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 12, 2023

Copper is an indispensable micronutrient for the development and replication of all eukaryotes, its redox properties are both harmful beneficial to cells. An imbalance in copper homeostasis thought be involved carcinogenesis. Importantly, cancer cell proliferation, angiogenesis, metastasis cannot separated from effects copper. Cuproposis a copper-dependent form death that differs other existing modalities regulatory death. The role cuproptosis pathogenesis nervous cardiovascular systems has been widely studied; however, impact on malignant tumors yet fully understood clinical perspective. Exploring signaling pathways related will undoubtedly provide new perspective anti-tumor drugs future. Here, we systematically review systemic cellular metabolic processes mechanisms cancer. In addition, discuss possibility targeting ion prolong survival patients, with emphasis most representative ionophores chelators. We suggest attention should paid potential value treatment specific cancers.

Language: Английский

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Potential Role of Natural Antioxidants in Countering Reperfusion Injury in Acute Myocardial Infarction and Ischemic Stroke

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1760 - 1760

Published: Sept. 13, 2023

Stroke and acute myocardial infarction are leading causes of mortality worldwide. The latter accounts for approximately 9 million deaths annually. In turn, ischemic stroke is a significant contributor to adult physical disability globally. While reperfusion crucial tissue recovery, it can paradoxically exacerbate damage through oxidative stress (OS), inflammation, cell death. Therefore, imperative explore diverse approaches aimed at minimizing ischemia/reperfusion injury enhance clinical outcomes. OS primarily arises from an excessive generation reactive oxygen species (ROS) and/or decreased endogenous antioxidant potential. Natural compounds counteract the mechanisms linked ROS. promising preclinical results, based on monotherapies, account protective effects against by ROS, translating these models into human applications has yielded controversial evidence. However, since wide spectrum antioxidants having chemical characteristics offers varied biological actions signaling pathways, multitherapy emerged as valuable therapeutic resource. Moreover, combination in holds potential synergistic effects. This study was designed with aim providing updated overview natural suitable preventing cerebral injuries.

Language: Английский

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Copper and Zinc Particles as Regulators of Cardiovascular System Function—A Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(13), P. 3040 - 3040

Published: July 5, 2023

Copper and zinc are micronutrients that play a crucial role in many cellular pathways, act as cofactors enzymatic systems, hence, modulate enzyme activity. The regulation of these elements homeostasis is precisely controlled by various mechanisms. Superoxide dismutase (SOD) an requiring both copper for proper functioning. Additionally, there interaction between the concentrations zinc. Dietary ingestion large amounts augments intestinal absorption this trace element, resulting deficiency secondary to excess. presence overabundance has detrimental impact on cardiovascular system; however, vascular contractility varies. plays modulation remodeling cardiac tissue, phenomenon cuproptosis been linked pathogenesis coronary artery disease. observable effect vasorelaxation mediated nitric oxide. maintenance levels within organism influences SOD essential myocardial ischemia/reperfusion injury. Recently, effects metal nanoparticles have investigated due their unique characteristics. On other hand, dietary introduction may result dysfunction, oxidative stress, DNA damage. intake affect function, but more research needed.

Language: Английский

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The crosstalk between mitochondrial quality control and metal-dependent cell death

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

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