Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 352 - 352

Published: March 15, 2024

Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation ferrous ions (Fe2+) and lipid peroxides. As metabolic hub body, liver crucial for iron storage metabolism. The seems to be closely related ferroptosis through Liver disease greatly threatens host health, exploring effective interventions essential. Mounting studies have demonstrated that one possible pathogenic mechanisms involved in disease. Targeting may provide a promising opportunity treating However, drugs targeting are extremely limited. Therefore, it urgent need develop new safe regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, recently shown great therapeutic potential via modulating ferroptosis-related genes or pathways. Here, we outline molecular mechanism systematically summarize regulatory function NAC on Finally, discuss application prospects problems concerning as regulators managing

Language: Английский

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Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115813 - 115813

Published: Nov. 2, 2023

Acute lung injury (ALI) is a major pathological problem characterized by severe inflammatory reactions and critical disease with high clinical morbidity mortality. Liensinine, isoquinoline alkaloid, extracted from the green embryos of mature Nelumbonaceae seeds. It has been reported to have an inhibitory effect on tumors. However, effects liensinine ALI not to-date. The aim this study was explore lipopolysaccharide (LPS)-induced its possible mechanism. We found that significantly reduced LPS-induced production factors IL-6, IL-8, TNF-α. In addition, blocked autophagic flux increased number autophagosomes upregulating LC3-II/I p62 protein levels. More importantly, pretreatment early stages autophagy inhibitor 3-Methyladenine (3-MA) can reverse secretion in ALI. PI3K/AKT/mTOR pathway involved regulated summary, suggests inhibits regulating via pathway, which may provide new therapeutic strategy alleviate

Language: Английский

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Editorial: Novel insights into liver injury: mechanisms, pathophysiology, and therapeutic strategies

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 18, 2025

Liver disease remains a major global health burden, with high morbidity and mortality rates (1). In recent years, continuous progress in biomedical fields such as immune regulation, biomarkers, new drug research development has brought opportunities for the diagnosis treatment of liver diseases. The complex interactions between diverse cell populations work together to maintain its function, ensuring effective clearance various infections abnormal cells (2). Furthermore, search specific biomarkers great significance diagnosis, prognosis assessment, monitoring Simultaneously, also hope Through in-depth study immunity, potential development, it is helpful better understand pathogenesis diseases, provide targets methods prevention, individualized treatment. Notably, our topic explores emerging regulatory mechanisms, therapeutic strategies, providing roadmap future clinical translation. Ananya et al. proposed that previous focuses on use prevent autoimmune while using blockers inhibit their activity or alter phenotypes reduce immunosuppressive properties tumor microenvironment. However, mechanism programmed death provided idea diseases (3). It been found there are ways cells, apoptosis, necroptosis, autophagy, pyroptosis ferroptosis. Proper regulation helps homeostasis, but imbalance may lead Immune can limit attack effects target organs through autophagy thus avoiding tissue damage (4,5). Secondly, excessive weaken body's ability fight infection increase susceptibility (6). This indirectly suggests precise pathway certain extent, protecting from further damage. become clear targeted modulation frontier area immunotherapy research. By enhancing survival function promotes reducing normal tissues (7). strategy applicable cancer, chronic infections, demonstrating good adaptability versatility. immune-mediated injury. Compared traditional modulation, this approach regulate system more selectively occurrence adverse effects.The affects progression almost all exploring crucial biomarker development.The discovery not only reflects status Currently, application metabolomics hereditary metabolic defects, tumors, cardiovascular psychiatric disorders other made rapid (14). future, these technologies will advance understanding complexity dynamics system, higher-level support advancement discovery, facilitate earlier entry into applications.

Language: Английский

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Ferroptosis as a key player in the pathogenesis and intervention therapy in liver injury: focusing on drug-induced hepatotoxicity

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

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Interaction between macrophages and ferroptosis: Metabolism, function, and diseases

Chinese Medical Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated several metabolic processes, including iron metabolism, and redox system. Macrophages are a group of innate immune cells that widely distributed throughout the body, play pivotal roles in maintaining balance its phagocytic efferocytotic effects. There profound association between biological functions macrophage ferroptosis. Therefore, this review aims to elucidate three key aspects unique relationship macrophages ferroptosis, metabolism their regulation cellular ferroptosis; ferroptotic stress modulates promotion inflammation; effects ferroptosis role diseases. Finally, we also summarize possible mechanisms regulating at global local levels, as well macrophage-mediated inflammatory process, provide new therapeutic insights for variety

Language: Английский

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Macrophage Perspectives in Liver Diseases: Programmed Death, Related Biomarkers, and Targeted Therapy

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 700 - 700

Published: June 14, 2024

Macrophages, as important immune cells of the organism, are involved in maintaining intrahepatic microenvironmental homeostasis and can undergo rapid phenotypic changes injured or recovering liver. In recent years, crucial role macrophage-programmed cell death development regression liver diseases has become a research hotspot. Moreover, macrophage-targeted therapeutic strategies emerging both preclinical clinical studies. Given macrophages’ vital complex organismal environments, there is tremendous academic interest developing novel that target these cells. This review provides an overview characteristics interactions between macrophage polarization, programmed death, related biomarkers, therapies. It aims to deepen understanding immunomodulation molecular mechanisms provide basis for treatment macrophage-associated diseases.

Language: Английский

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Ferroptosis‐modulating natural products for targeting inflammation-related diseases: Challenges and opportunities in manipulating redox signaling

Antioxidants and Redox Signaling, Journal Year: 2024, Volume and Issue: 41(13-15), P. 976 - 991

Published: July 13, 2024

Numerous disorders are linked to ferroptosis, a form of programmed cell death triggered by lipid peroxidation accumulation rather than apoptosis. Inflammation is the body's defensive response stimuli and also caused inflammatory chemicals that can harm body. The treatment diseases focusing on signaling pathways mechanisms ferroptosis has emerged as new area worthy extensive research.

Language: Английский

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Methods for Monitoring NCOA4-Mediated Ferritinophagy

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 177 - 189

Published: Jan. 1, 2024

Language: Английский

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