Cuproptosis: mechanisms and links with cancers

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Language: Английский

---

Deadly excess copper

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103256 - 103256

Published: June 28, 2024

Higher eukaryotes' life is impossible without copper redox activity and, literally, every breath we take biochemically demonstrates this. However, this dependence comes at a considerable price to ensure target-oriented action. Thereto its uptake, distribution but also excretion are executed by specialized proteins with high affinity for the transition metal. Consequently, malfunction of enzymes/transporters, as case in hereditary Wilson disease that affects intracellular transporter ATP7B, serious cellular damage. One hallmark progressive accumulation, primarily liver brain becomes deadly if left untreated. Such excess toxicity may result from accidental ingestion or attempted suicide. Recent research has shed new light into cell-toxic mechanisms and affected targets processes such even be exploited respect cancer therapy. Moreover, therapies currently under development fight against toxic copper.

Language: Английский

---

The physiological and pathophysiological roles of copper in the nervous system

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(1), P. 3505 - 3543

Published: May 15, 2024

Abstract Copper is a critical trace element in biological systems due the vast number of essential enzymes that require metal as cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine‐ β ‐hydroxylase. Due its key role oxidative metabolism, antioxidant defence neurotransmitter synthesis, copper particularly important for neuronal development proper function. Moreover, increasing evidence suggests also serves functions synaptic network activity, regulation circadian rhythms, arousal. However, it to note because copper's ability redox cycle generate reactive species, cellular levels must be tightly regulated meet needs while avoiding copper‐induced stress. Therefore, intricate system transporters, exporters, chaperones trafficking proteins function properly coordinate fashion. Indeed, disorders metabolism such Menkes disease Wilson disease, well diseases linked dysfunction copper‐requiring enzymes, SOD1‐linked amyotrophic lateral sclerosis, demonstrate dramatic neurological consequences altered homeostasis. In this review, we explore physiological importance nervous pathologies related improper handling.

Language: Английский

---

Cuproplasia and cuproptosis, two sides of the coin

Cancer Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Abstract Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evasion, and so on by reprogramming regulatory network, defined cuproplasia. Thus, targeting chelation reduce levels has been considered rational therapy strategy. However, overloaded ions could be toxic, which leads aggregation lipoylated mitochondrial proteins depletion iron‐sulfur clusters, ultimately resulting death, termed cuproptosis. Upon its discovery, cuproptosis attracted great interest from oncologists, ionophores exhibits potential anti‐tumor therapy. In this review, we present underlying mechanisms involved cuproplasia Additionally, sum up chemicals either or cancer Further attention should paid distinguishing patients who are suitable

Language: Английский

---

The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16

Published: Oct. 4, 2022

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, antioxidant defense. level has been proved to be closely related the morbidity mortality of cardiovascular diseases such as atherosclerosis, heart failure, diabetic cardiomyopathy (DCM). deficiency can induce cardiac hypertrophy aggravate cardiomyopathy, while copper excess mediate types cell death, autophagy, apoptosis, cuproptosis, pyroptosis, fibrosis. Both lead redox imbalance, activate inflammatory response, cardiomyopathy. This defective metabolism suggests a specific metabolic pattern in diabetes role pathogenesis progression DCM. review aimed at providing timely summary effects homeostasis on DCM discussing potential underlying molecular mechanisms.

Language: Английский

---

MAMMALIAN COPPER HOMEOSTASIS: PHYSIOLOGIC ROLES AND MOLECULAR MECHANISMS

Physiological Reviews, Journal Year: 2024, Volume and Issue: 105(1), P. 441 - 491

Published: Aug. 22, 2024

In the past decade, evidence for numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries Cu involvement cell signaling, autophagy, motility, differentiation, and regulated death (cuproptosis) have markedly extended list already known functions Cu, such as a cofactor essential metabolic enzymes, protein structural component, regulator trafficking. Novel unexpected transporting proteins enzymes been identified, new disorders homeostasis described. Significant progress made mechanistic studies two classic metabolism, Menkes disease Wilson’s disease, which paved way novel approaches to their treatment. discovery cuproptosis role metastatic growth increased interest targeting homeostatic pathways treat cancer. this review, we summarize established concepts field discuss how decade expand modify these concepts. brain metabolism functional speciation recently discovered attracted significant attention are highlighted review.

Language: Английский

---

Cuproptosis in lung cancer: mechanisms and therapeutic potential

Molecular and Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 479(6), P. 1487 - 1499

Published: July 22, 2023

Language: Английский

---

Copper trafficking systems in cells: insights into coordination chemistry and toxicity

Dalton Transactions, Journal Year: 2023, Volume and Issue: 52(42), P. 15277 - 15296

Published: Jan. 1, 2023

This review describes the coordination chemistry of a copper trafficking system and toxicity mechanisms arising from impaired homeostasis.

Language: Английский

---

Copper in melanoma: at the crossroad of protumorigenic and anticancer roles

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103552 - 103552

Published: Feb. 15, 2025

Language: Английский

---

Cu(I) chelators: Useful tools to reveal and control Cu(I) homeostasis and toxicity

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 539, P. 216684 - 216684

Published: April 24, 2025

Language: Английский

---