The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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Ferritinophagy: research advance and clinical significance in cancers

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Dec. 18, 2023

Ferritinophagy, a process involving selective autophagy of ferritin facilitated by nuclear receptor coactivator 4 (NCOA4), entails the recognition NCOA4 and subsequent delivery to autophagosome. Within autophagosome, undergoes degradation, leading release iron in lysosome. It is worth noting that excessive levels can trigger cell death. Recent evidence has elucidated significant roles played ferritinophagy ferroptosis regulation initiation progression cancer. Given crucial role tumor biology, it may serve as potential target for future anti-tumor therapeutic interventions. In this study, we have provided distinctive features its distinctions from ferroptosis. Moreover, briefly examined fundamental regulatory mechanisms ferritinophagy, encompassing involvement specific NCOA4, Nrf2/HO-1 signaling other pathways. Subsequently, synthesized current understanding impact on cancer applications, with particular emphasis utilization chemotherapy, nanomaterials, immunotherapy pathway purposes.

Language: Английский

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Iron as a therapeutic target in chronic liver disease

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(4), P. 616 - 655

Published: Jan. 20, 2023

It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor development and progression of disease. The recent clarification ferroptosis as specific form regulated hepatocyte death different from apoptosis description ferritinophagy variation autophagy prompted detailed investigations on association liver. In this review, we will present brief discussion absorption handling by with emphasis role macrophages significance regulators hepcidin, transferrin, ferritin homeostasis. regulation endogenous exogenous mod-ulators examined. Furthermore, involvement various diseases including alcoholic non-alcoholic disease, chronic hepatitis B C, fibrosis, hepatocellular carcinoma (HCC) analyzed. Finally, experimental clinical results following interventions to reduce promising manipulation presented. Most benefited inhibition using inhibitors notable exception HCC, where induction is desired effect. Current evidence mostly stems vitro vivo studies need for well-designed future trials warranted.

Language: Английский

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Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2668 - 2668

Published: Feb. 25, 2024

Hemochromatosis represents clinically one of the most important genetic storage diseases liver caused by iron overload, which is to be differentiated from hepatic overload due excessive release erythrocytes in patients with hemolytic disorders. This disorder under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), gut microbiome, and alcohol abuse as a risk factor, are all topics this review article. Triggered released intracellular free ferritin via autophagic process ferritinophagy, ferroptosis involved hemochromatosis specific form iron-dependent regulated cell death. develops course mitochondrial injury associated additional accumulation, followed production ROS lipid peroxidation. A low fecal content during therapeutic depletion reduces colonic inflammation oxidative stress. In clinical terms, an essential trace element required for human health. Humans cannot synthesize must take it up iron-containing foods beverages. Under physiological conditions, healthy individuals allow homeostasis restricting extent intestinal depending on realistic demand, avoiding uptake excess. For condition, body has no chance adequately compensate through removal. hemochromatosis, molecular finetuning set off mutations high-FE2+ (HFE) genes that lead lack hepcidin or resistance part ferroportin binding. major mechanism increased stores body. Hepcidin liver-derived peptide, impairs enterocytes macrophages interacting ferroportin. As result, accumulates various organs including liver, severely injured causes hemochromatosis. diagnosis difficult establish uncharacteristic features. Among these asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, cardiopathy. Diagnosis initially suspected serum levels ferritin, non-specific parameter also elevated inflammatory excluded safer diagnostic side. facilitated if combined fasting transferrin saturation, testing, family screening. Various attempts were published algorithms. However, none based evidence quantitative results derived scored key features opposed other known complex diseases. autoimmune hepatitis (AIH) drug-induced (DILI). both diseases, algorithms used line artificial intelligence (AI) principles ascertain diagnosis. The first-line therapy involves regular life-long phlebotomy remove blood, improves prognosis may prevent development end-stage disease such cirrhosis hepatocellular carcinoma. Liver transplantation rarely performed, confined acute failure. conclusion, ROS, concomitant play contributing role requires early initiation treatment.

Language: Английский

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The Role of Hepcidin in Myelodysplastic Syndromes (MDS): A Systematic Review of Observational Studies

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 332 - 332

Published: Jan. 11, 2024

Iron overload emerges as a serious complication in myelodysplastic syndromes (MDS), particularly associated with frequent transfusions during the course of disease. The discovery and description hepcidin's mechanisms action have contributed to deeper understanding iron metabolism. existing literature reports potential role hepcidin MDS, yet these data are fragmented presented an unstructured, somewhat chaotic manner. Hence, address data, we performed systematic review observational studies examining levels MDS. An extensive three bibliographic databases (Pubmed, Web Science, Scopus) enabled us identify 12 studies. These focused primarily on adult patients low-risk MDS who underwent chelation therapy. in-depth analysis manuscripts led four main conclusions: (1) although high serum most generally not found significant difference between healthy individuals; (2) specific type; (3) strongly genetic status patients; (4) high-risk is levels. While furnished comprehensive summary significance there still gaps that future research should address. This pertains capacity predicting adverse outcomes for evaluating efficacy therapy or need transfusion.

Language: Английский

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Iron homeostasis and insulin sensitivity: unraveling the complex interactions

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Language: Английский

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Emerging Insights: miRNA Modulation of Ferroptosis Pathways in Lung Cancer

Experimental Cell Research, Journal Year: 2024, Volume and Issue: 442(2), P. 114272 - 114272

Published: Oct. 1, 2024

Language: Английский

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The impact of inflammation and acute phase activation in cancer cachexia

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

Published: Oct. 31, 2023

The development of cachexia in the setting cancer or other chronic diseases is a significant detriment for patients. Cachexia associated with decreased ability to tolerate therapies, reduction ambulation, reduced quality life, and increased mortality. appears intricately linked activation acute phase response drain on metabolic resources. Work has begun focus important inflammatory factors their role immune cachexia. Furthermore, data supporting liver, lung, skeletal muscle, tumor as all playing are emerging. Although increasingly being recognized involved cachexia, work understanding underlying mechanisms remains an active area investigation still lack holistic clear causal link. Studies date largely correlative nature, nonetheless suggesting possibility various reactants. Herein, we examine current literature regarding proteins, evidence these proteins play promotion exacerbation therapeutic potential

Language: Английский

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Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: April 5, 2024

Abstract The disease-specific accumulation of pathological proteins has long been the major focus research in neurodegenerative diseases (ND), including Alzheimer’s disease (AD) and related dementias (RD), but recent identification a multitude genetic risk factors for ND immune-associated genes highlights importance immune processes pathogenesis progression. Studies animal models have characterized local response to AD ADRD, due complexity co-existence multiple protein pathologies human donor brains, precise role is far from understood. To better characterize interplay between different extracellular intracellular brain’s intrinsic system ND, we set out comprehensively profile postmortem brain samples individuals with “pure” beta-Amyloid tau pathology (AD), α-Synuclein Lewy body (LBD), as well cases neuropathological changes (ADNC) (MIX). Combining immunohistochemical profiling microglia digital image analysis, along deep immunophenotyping using gene expression on NanoString nCounter® platform spatial GeoMx® identified robust activation signature samples. This maintained persons mixed pathologies, irrespective (LB) pathology, while LBD LB exhibit an attenuated distinct signature. Our studies highlight disease- region-specific profiles further underscore neuroimmune interactions ND.

Language: Английский

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Bortezomib elevates intracellular free Fe2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 to inhibit multiple myeloma cells

Annals of Hematology, Journal Year: 2024, Volume and Issue: 103(9), P. 3627 - 3637

Published: April 22, 2024

Language: Английский

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