Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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In situ hydrogel based on Cu–Fe3O4 nanoclusters exploits oxidative stress and the ferroptosis/cuproptosis pathway for chemodynamic therapy

Biomaterials, Год журнала: 2024, Номер 311, С. 122675 - 122675

Опубликована: Июнь 26, 2024

Язык: Английский

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Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4753 - 4753

Опубликована: Апрель 26, 2024

Wilson disease is a genetic disorder of the liver characterized by excess accumulation copper, which found ubiquitously on earth and normally enters human body in small amounts via food chain. Many interesting details were published mechanistic steps, such as generation reactive oxygen species (ROS) cuproptosis causing copper dependent cell death. In patients with disease, also, increased iron deposits that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes subcellular organelles. All topics are covered this review article, addition diagnostic therapeutic issues disease. Excess Cu2+ primarily leads (ROS), evidenced early experimental studies exemplified detection hydroxyl radical formation using electron spin resonance (ESR) spin-trapping method. The ROS products follows principles Haber–Weiss reaction subsequent Fenton leading copper-related cuproptosis, thereby closely connected ROS. Copper due impaired biliary excretion caused inheritable malfunctioning or missing ATP7B protein. As result, disturbed cellular homeostasis prevails liver. Released from cells limited storage capacity, toxic circulation arrives at other organs, local injury. This explains why injures not only liver, but also brain, kidneys, eyes, heart, muscles, bones, explaining multifaceted clinical features Among these depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser–Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, arthralgia. addition, Coombs-negative hemolytic anemia key feature undetectable serum haptoglobin. modified Leipzig Scoring System helps diagnose Patients well-treated first-line chelators like D-penicillamine facilitate removal circulating bound albumin increase urinary excretion. Early chelation therapy improves prognosis. Liver transplantation an option viewed ultima ratio end-stage untreatable complications acute failure. finally thus be life-saving approach curative treatment replacing hepatic gene mutation. conclusion, representing molecular challenge.

Язык: Английский

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Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials

Cancers, Год журнала: 2024, Номер 16(3), С. 512 - 512

Опубликована: Янв. 24, 2024

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, oxidative stress. The emergence of ferroptosis cuproptosis as distinct forms non-apoptotic death has heightened their significance, particularly connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence cuproptosis. Studies reveal a link between accumulation induction. This interconnected relationship presents promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing toxicity iron clinical settings becomes crucial. Simultaneous targeting cuproptosis, exemplified combination sorafenib elesclomol-Cu, represents an intriguing approach. Strategies mitochondria further enhance precision approaches, providing hope improving treatment outcomes drug-resistant cancers. Moreover, chelators copper-lowering agents established therapeutic modalities exhibits synergy that holds promise augmentation anti-tumor efficacy malignancies. review elaborates on complex interplay underlying mechanisms, explores potential druggable targets both research settings.

Язык: Английский

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Cuproptosis: unveiling a new frontier in cancer biology and therapeutics

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 1, 2024

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.

Язык: Английский

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Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7544 - 7544

Опубликована: Июль 9, 2024

Ferroptosis is a type of nonapoptotic cell death that characteristically caused by phospholipid peroxidation promoted radical reactions involving iron. Researchers have identified many the protein factors are encoded genes promote ferroptosis. Glutathione peroxidase 4 (GPX4) key enzyme protects phospholipids from and suppresses ferroptosis in glutathione-dependent manner. Thus, dysregulation involved cysteine and/or glutathione metabolism closely associated with From perspective dynamics, actively proliferating cells more prone to than quiescent cells, which suggests species generated during oxygen-involved responsible for lipid peroxidation. Herein, we discuss initial events dominantly occur process energy metabolism, association deficiency. Accordingly, tricarboxylic acid cycle coupled respiratory chain mitochondria main subjects here, this likely source both electrons free Since not only carbohydrates, but also amino acids, especially glutamate, major substrates central dealing nitrogen derived groups contributes subject discussion.

Язык: Английский

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Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies

Cancers, Год журнала: 2024, Номер 16(6), С. 1220 - 1220

Опубликована: Март 20, 2024

Based on the multifaceted molecular machinery that tightly controls iron cellular homeostasis, this review delves into its paradoxical, potentially dangerous role in biological systems, with a special focus double-edged sword correlations cancer. Indeed, though is vital micronutrient and required cofactor participating several essential cell functions, tendency to cause oxidative stress can be related both cancer risk activation of death pathways. In scenario, ferroptosis refers an iron-dependent form regulated (RCD) powered by overload lethal peroxides sharing distinctive oxidized phospholipid profiles. As unique pathway, morphologically mechanistically different from other types programmed involving executioner family proteins. The accumulation cytotoxic lipid encompasses antagonism between execution defense occurring when ferroptosis-promoting activities significantly exceed antioxidant defenses. most recent breakthroughs have aroused great consideration tumor biology, as targeting provide new tools for exploring therapeutic strategies suppression. Mutations death/survival pathway alterations, well metabolic regulations cells, including propensity generate ROS, are seen features render cells unprotected ferroptosis, thereby exposing vulnerabilities which deserve further attention regarded targetable cancers limited options.

Язык: Английский

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A facile green synthesis of photoluminescent carbon dots using Pumpkin seeds for ultra-sensitive Cu2+ and Fe3+ ions detection in living cells

Journal of Molecular Structure, Год журнала: 2024, Номер 1312, С. 138543 - 138543

Опубликована: Май 4, 2024

Язык: Английский

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Hesperetin alleviates aflatoxin B1 induced liver toxicity in mice: Modulating lipid peroxidation and ferritin autophagy

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 284, С. 116854 - 116854

Опубликована: Авг. 13, 2024

One of the ways Aflatoxin B1 damages liver is through ferroptosis. Ferroptosis characterized by build-up lipid peroxides and reactive oxygen species (ROS) due to an excess iron. Dietary supplements have emerged as a promising strategy for treating ferroptosis in liver. The flavonoid component hesperetin, which mostly present citrus fruits, has number pharmacological actions, such those against fibrosis, cancer, hyperglycemia. However, hesperetin's effects mechanisms hepatic are still unknown. In this study, 24 male C57BL/6 J mice were randomly assigned CON, AFB1 (0.45 mg/kg/day), AFB1+ hesperetin treatment groups (40 mg/kg/day). results showed that improved structural damage mouse liver, down-regulated inflammatory factors (Cxcl1, Cxcl2, CD80, F4/80), alleviated fibrosis induced aflatoxin B1. Hesperetin reduced peroxidation iron accumulation up-regulating levels antioxidant enzymes (GPX4, GSH-Px, CAT, T-AOC). It worth noting not only but also maintained dynamic balance ions reducing ferritin autophagy. Mechanistically, ability regulate autophagy depends on PI3K/AKT/mTOR/ULK1 pathway. AFB1-induced HepG2 cells, addition PI3K inhibitor (LY294002) AKT (Miransertib) confirmed regulated pathway inhibit degradation lysosomes. summary, our suggest regulates system inhibits hyperautophagy, thereby mitigate peroxidation. This work provides fresh perspective mechanism behind mice.

Язык: Английский

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Melatonin protects against cadmium-induced endoplasmic reticulum stress and ferroptosis through activating Nrf2/HO-1 signaling pathway in mice lung

Food and Chemical Toxicology, Год журнала: 2025, Номер unknown, С. 115324 - 115324

Опубликована: Фев. 1, 2025

Язык: Английский

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