Targeting ferroptosis: a new therapeutic opportunity for kidney diseases

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 3, 2024

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and characterized by the accumulation lipid peroxides to lethal levels. involves multiple pathways including redox balance, regulation, mitochondrial function, amino acid, lipid, glycometabolism. Furthermore, various disease-related signaling also play role in regulating process oxidation. In recent years, with emergence concept ferroptosis in-depth study its mechanisms, closely associated biological conditions related kidney diseases, organ development, aging, immunity, cancer. This article reviews development ferroptosis, mechanisms (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, MBOAT1/2 pathways), latest research progress involvement diseases. It summarizes diseases within frameworks metabolism, reactive oxygen biology, biology. The introduces key regulatory factors as well important concepts major open questions natural compounds. hoped future research, further breakthroughs can be made understanding regulation mechanism utilizing promote treatments for such acute injury(AKI), chronic disease (CKD), diabetic nephropathy(DN), renal carcinoma. paves way new approach prevent, treat clinical

Language: Английский

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Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 2485 - 2529

Published: June 1, 2024

Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess iron accumulation and lipid peroxidation-induced damage. There growing body evidence indicating that ferroptosis plays critical role in the advancement tumors. The increased metabolic activity higher levels tumor cells make them particularly vulnerable to ferroptosis. As result, targeted induction becoming increasingly promising approach for cancer treatment. This review offers overview regulatory mechanisms ferroptosis, delves into mechanism action traditional small molecule inducers their effects on various In addition, latest progress inducing using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic (SDT) nanomaterials summarized. Finally, this discusses challenges opportunities development ferroptosis-inducing agents, focusing discovering targets, improving selectivity, reducing toxic side effects. Keywords: inducers, molecules, PROTACs, PDT, SDT,

Language: Английский

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Qizhu Jianwei decoction triggers ferroptosis by exosome-mediated miR-199-3p/ACSL4 signaling pathways

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119529 - 119529

Published: Feb. 1, 2025

Language: Английский

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Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies

Life Sciences, Journal Year: 2024, Volume and Issue: 346, P. 122629 - 122629

Published: April 15, 2024

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs other forms death, such as apoptosis necrosis. Molecular therapeutics have hard time playing the long-acting role ferroptosis induction due to their limited water solubility, low targeting capacity, quick metabolism vivo. To this end, small molecule inducers based on biological factors long been used strategy induce death. Research into advancements nanotechnology led discovery that nanomaterials are superior medications triggering ferroptosis. Nanomaterials derived iron can enhance by directly releasing large quantities increasing ROS levels. Moreover, utilizing promote programmed minimizes probability unfavorable effects induced mutations cancer-associated genes RAS TP53. Taken together, review summarizes molecular mechanisms involved along with classification induction. also emphasized importance organelles control cancer therapy. The trigger categorized explained. Iron-based noniron-based characterization at cellular levels explored, which will be useful for inducing leads reduced tumor growth. Within framework, we offer synopsis, traverses well-established mechanism offers practical suggestions design therapeutic use nanomaterials.

Language: Английский

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Notoginsenoside R1 treatment facilitated Nrf2 nuclear translocation to suppress ferroptosis via Keap1/Nrf2 signaling pathway to alleviated high-altitude myocardial injury

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116793 - 116793

Published: May 21, 2024

High-altitude myocardial injury (HAMI) represents a critical form of altitude illness for which effective drug therapies are generally lacking. Notoginsenoside R1, prominent constituent derived from Panax notoginseng, has demonstrated various cardioprotective properties in models ischemia/reperfusion injury, sepsis-induced cardiomyopathy, cardiac fibrosis, and injury. The potential utility notoginsenoside R1 the management HAMI warrants prompt investigation. Following successful construction model, series experimental analyses were conducted to assess effects at dosages 50 mg/Kg 100 mg/Kg. results indicated that exhibited protective against hypoxic by reducing levels CK, CK-MB, LDH, BNP, leading improved function decreased incidence arrhythmias. Furthermore, was found enhance Nrf2 nuclear translocation, subsequently regulating SLC7A11/GPX4/HO-1 pathway iron metabolism mitigate ferroptosis, thereby mitigating inflammation oxidative stress induced high-altitude conditions. In addition, application ML385 confirmed involvement translocation therapeutic approach HAMI. Collectively, advantageous impacts on have been linked suppression ferroptosis via signaling.

Language: Английский

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Targeting Ferroptosis as an Advance Strategy in Cancer Therapy

Antioxidants and Redox Signaling, Journal Year: 2024, Volume and Issue: 41(10-12), P. 616 - 636

Published: July 3, 2024

This study innovates by systematically integrating the molecular mechanisms of iron death and its application in cancer therapy. By deeply analyzing interaction between tumor microenvironment, provides a new theoretical basis for treatment directions developing more effective strategies. In addition, points to critical issues barriers that need be addressed future research, providing valuable insights into use clinical translation.

Language: Английский

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Ferroptosis-Related Oxaliplatin Resistance in Multiple Cancers: Potential Roles and Therapeutic Implications

Heliyon, Journal Year: 2024, Volume and Issue: 10(18), P. e37613 - e37613

Published: Sept. 1, 2024

Oxaliplatin (OXA)-based therapy is effective in the treatment of multiple cancers. However, primary or acquired OXA resistance remains an emerging challenge for its clinical application. Ferroptosis iron-dependent mode cell death that has been demonstrated to play essential role chemoresistance many drugs, including OXA. In particular, dysregulation SLC7A11-GPX4, one major antioxidant systems ferroptosis, was found colorectal cancer (CRC) and hepatocellular carcinoma (HCC). addition, Nrf2, upstream regulator GPX4 other factors, also involved CRC HCC. Inhibition SLC7A11-GPX4 Nrf2 by genetic deletion pharmaceutical inhibition could significantly reverse resistance. Long noncoding RNA (lncRNA) participates ferroptosis cells. Specifically, LINC01134 promotes recruitment promoter GPX4, thereby exerting transcriptional regulation which eventually increases sensitivity HCC through upregulation ferroptosis. On hand, a novel lncRNA DACT3-AS1 sensitizes gastric cells miR-181a-5p/sirtuin 1(SIRT1)-mediated Therapies based on combination enhancers provide new therapeutic insights overcome present review, we current understanding ferroptosis-related resistance, highlight pathogenesis chemoresistance, summarize available therapies target enhancing

Language: Английский

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Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6083 - 6083

Published: May 31, 2024

Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis exosomes modulate development but rarely investigated natural product treatments their modulating miRNAs. This review focuses on ferroptosis-modulating effects of products miRNAs concerning participation exosome biogenesis (secretion assembly)-related targets cells. Natural with were retrieved organized. Next, a literature search established connection panel genes these ferroptosis-associated products. Moreover, inputted into miRNA database (miRDB) bioinformatically potential for modulation biogenesis. Finally, provided Consequently, connections from ferroptosis–miRNA–exosome product-based anticancer are well-organized. sheds light research directions integrating therapeutic diseases.

Language: Английский

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Portable Cell Tracking Velocimetry for Quantification of Intracellular Fe Concentration of Blood Cells

Micromachines, Journal Year: 2025, Volume and Issue: 16(2), P. 126 - 126

Published: Jan. 23, 2025

Hematological analysis is crucial for diagnosing and monitoring blood-related disorders. Nevertheless, conventional hematology analyzers remain confined to laboratory settings due their high cost, substantial space requirements, maintenance needs. Herein, we present a portable cell tracking velocimetry (CTV) device the precise measurement of magnetic susceptibility biological entities at single-cell level, focusing on red blood cells (RBCs) in this work. The system integrates microfluidic channel positioned between permanent magnets that generate well-defined field gradient (191.82 TA/mm2). When are injected into chamber, particular response recorded used estimate properties quantify intracellular hemoglobin (Hb) concentration. We successfully track over 400 RBCs per condition using imaging trajectory analysis, enabling detailed characterizations physical properties. A comparison mean corpuscular measurements revealed strong correlation our CTV standard ultraviolet-visible (UV-Vis) spectrophotometry (23.1 ± 5.8 pg vs. 22.4 3.9 pg, p > 0.05), validating accuracy measurements. system's resolution reveals population distributions unobtainable through bulk methods. Thus, technology provides rapid, label-free approach characterization, offering new possibilities point-of-care hematological field-based research applications.

Language: Английский

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Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 25, 2025

Abstract The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and activities of digestive organs. Additionally, muscle tissues serve an endocrine function secreting myogenic cytokines, thereby regulating metabolism throughout entire body. Maintaining requires iron homeostasis. Recent studies suggest that disruptions ferroptosis, form iron-dependent cell death, are essential contributors to progression wide range diseases disorders, including sarcopenia, cardiomyopathy, amyotrophic lateral sclerosis. Thus, comprehensive overview mechanisms ferroptosis these conditions is crucial for identifying potential therapeutic targets developing new strategies disease treatment and/or prevention. This review aims summarize recent advances understanding molecular underlying context injury, as well associated disorders. Moreover, we discuss within pathway possible managing Finally, shed light on current limitations future prospects interventions targeting ferroptosis.

Language: Английский

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