Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(22), P. 8765 - 8765

Published: Nov. 20, 2020

Ferroptosis is a type of cell death that was described less than decade ago. It caused by the excess free intracellular iron leads to lipid (hydro) peroxidation. Iron essential as redox metal in several physiological functions. The brain one organs known be affected homeostatic balance disruption. Since 1960s, increased concentration central nervous system has been associated with oxidative stress, oxidation proteins and lipids, death. Here, we review main mechanisms involved process ferroptosis such peroxidation, glutathione peroxidase 4 enzyme activity, metabolism. Moreover, association pathophysiology some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, Huntington’s also addressed.

Language: Английский

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ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(6), P. 1439 - 1451

Published: May 2, 2023

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells

Advanced Science, Journal Year: 2021, Volume and Issue: 8(22)

Published: Oct. 10, 2021

Abstract Ferroptosis is a new form of regulated cell death, which characterized by the iron‐dependent accumulation lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid cycle are regulation key ferroptosis markers reduced nicotinamide adenine dinucleotide (NADPH), glutathione (GSH), reactive oxygen species (ROS), therefore imposing potential regulatory roles ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit for self‐preservation upregulation glycolysis PPP. Due rapid proliferation intensified rate, has become target disrupting redox homeostasis induce Based on these emerging insights, impact those‐tumor specific aberrations systematically characterized, rewired glucose compensation through glutamine utilization analyzed underlying molecular mechanisms. Additionally, those ferroptosis‐based therapeutic strategies also discussed exploiting vulnerabilities, may open up avenues treatment clinical context.

Language: Английский

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Molecular mechanisms of ferroptosis and their involvement in brain diseases

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 244, P. 108373 - 108373

Published: March 8, 2023

Ferroptosis is a type of regulated cell death characterized by intracellular accumulation iron and reactive oxygen species, inhibition system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation lipid peroxidation. Since its discovery characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, involvement disease pathways. inducers include erastin, sorafenib, sulfasalazine glutamate, which, inhibiting prevent import cysteine into cells. RSL3, statins, Ml162 Ml210 induce ferroptosis peroxidase 4 (GPX4), which responsible for preventing formation peroxides, FIN56 withaferin trigger GPX4 degradation. On other side, inhibitors ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 BH4, interrupt peroxidation cascade. Additionally, deferoxamine, deferiprone N-acetylcysteine, targeting cellular pathways, also classified as inhibitors. Increased evidence has established distinct brain diseases, including Alzheimer's, Parkinson's Huntington's amyotrophic lateral sclerosis, multiple Friedreich's ataxia. Thus, deep understanding how contributes these it can be modulated, open new window opportunities novel therapeutic strategies targets. Other studies shown sensitivity cancer cells with mutated RAS induction that chemotherapeutic agents synergize tumor treatment. tempting consider may arise target mechanistic pathway treatment tumors. Therefore, this work provides an up-to-date review on molecular mechanisms their diseases. In addition, information main targets provided.

Language: Английский

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Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Cancers, Journal Year: 2021, Volume and Issue: 13(5), P. 986 - 986

Published: Feb. 27, 2021

It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven aberrant cell growth. Cancer can adapt maintain redox homeostasis through a variety mechanisms. The prevalent perception about ROS is they one the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants aim mitigate stress have tested for prevention or treatment, although effectiveness strategy yet be established. In recent years, it increasingly appreciated complex, multifaceted role in microenvironment (TME), targeted amplify inside cause destruction. Accumulating evidence indicates immunotherapies alter intensify resulting ROS-dependent rejection. Herein we review progresses regarding impact various immune TME, discuss emerging ROS-modulating strategies used combination with achieve enhanced antitumor effects.

Language: Английский

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ROS induced lipid peroxidation and their role in ferroptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 1, 2023

Reactive oxygen species (ROS) play a crucial part in the process of cell death, including apoptosis, autophagy, and ferroptosis. ROS involves oxidation lipids generate 4-hydroxynonenal other compounds associated with it. Ferroptosis may be facilitated by lipid peroxidation phospholipid bilayers. In order to offer novel ideas directions for investigation disorders connected these processes, we evaluate function which ultimately leads ferroptosis as well proposed crosstalk mechanisms between types programmed death.

Language: Английский

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Blockade of GCH1/BH4 Axis Activates Ferritinophagy to Mitigate the Resistance of Colorectal Cancer to Erastin-Induced Ferroptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Feb. 10, 2022

Ferroptosis, a type of cell death triggered by excessive accumulation iron-dependent lipid peroxidation, possesses an excellent potential in cancer treatment. However, many colorectal (CRC) lines are resistant to ferroptosis induced erastin and RSL3, the classical ferroptotic inducers. Moreover, underlying mechanism resistance remains poorly elucidated. This study sought discover major factor contributing CRC. The findings will help design strategies for triggering application individualized tumor therapy. Here, we show that tetrahydrobiopterin (BH4) determines sensitivity CRC cells erastin. GTP cyclohydrolase-1 (GCH1) is first rate-limiting enzyme BH4. Genetic or pharmacological inhibition GCH1 decreased BH4 assisted induction, peroxidation enhancement, ferrous iron accumulation. supplementation completely inhibited features resulting from knockdown. Unexpectedly, knockdown failed enhance RSL3-induced Mechanistically, drastically activated ferritinophagy during treatment rather than RSL3 Administration autophagy inhibitor reversed GCH1-knockdown cells. co-treatment vivo synergistically growth Overall, our results identified GCH1/BH4 metabolism as burgeoning defense Inhibiting promoted erastin-induced activating ferritinophagy, suggesting combining inhibitors with novel therapeutic strategy.

Language: Английский

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Targeting ferroptosis in acute kidney injury

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(2)

Published: Feb. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Language: Английский

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The molecular mechanisms of ferroptosis and its role in cardiovascular disease

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 145, P. 112423 - 112423

Published: Nov. 17, 2021

Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. shows unique characteristics in biology, chemistry, gene levels, compared to other forms. The metabolic disorder intracellular LOOH catalyzed iron causes the inactivity GPX4, disrupts balance, triggers death. Metabolism amino acid, iron, lipid, including associated pathways, considered as specific hallmark ferroptosis. Epidemiological studies animal experiments have shown that ferroptosis plays an important character pathophysiology cardiovascular disease such atherosclerosis, myocardial infarction (MI), ischemia/reperfusion (I/R), heart failure (HF), cardiac hypertrophy, cardiomyopathy, abdominal aortic aneurysm (AAA). This review systematically summarized latest research progress on mechanisms Then we report contribution diseases. Finally, discuss analyze therapeutic approaches targeting for with

Language: Английский

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