GPX4, ferroptosis, and diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 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

Language: Английский

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Nitroxidative Stress, Cell—Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2050 - 2050

Published: Feb. 26, 2025

Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative nitrosative stress, an imbalance between reactive oxygen nitrogen species (ROS/RNS) antioxidant defenses, plays crucial role in its pathophysiology. While are essential for physiological functions, excessive levels can cause cellular component neuronal dysfunction pain. This review highlights the complex interactions species, systems, cell signaling, neuropathic We discuss roles ROS/RNS detrimental effects oxidative stress. Furthermore, we explore potential manganese porphyrins, compounds with properties, as promising therapeutic agents mitigate stress alleviate pain by targeting key pathways involved Further research is needed fully understand their managing human non-human animals.

Language: Английский

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Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155738 - 155738

Published: June 1, 2024

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, autophagy, characterised by iron, reactive oxygen species, lipid peroxide accumulation, as well glutathione (GSH) depletion GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis the onset progression respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, fibrosis, cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in treatment owing natural properties potential efficacy. These can effectively regulate modulating several key signalling pathways such system Xc

Language: Английский

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Stress/cell death pathways, neuroinflammation, and neuropathic pain

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 33 - 51

Published: Sept. 8, 2023

Summary Neuropathic pain is a common and debilitating modality of chronic induced by lesion or disease the somatosensory nervous system. Albeit elucidation numerous pathophysiological mechanisms development potential treatment compounds, safe reliable therapies neuropathic remain poor. Multiple stress/cell death pathways have been shown to be implicated in neuroinflammation during pain. Here, we summarize current knowledge present an overview roles molecular pain, covering intrinsic extrinsic apoptosis, autophagy, mitophagy, ferroptosis, pyroptosis, necroptosis, phagoptosis. Small molecule compounds that modulate alleviating are discussed mainly based on preclinical models. These findings will contribute in‐depth understanding pathological processes as well bridge gap between basic translational research uncover new neuroprotective interventions.

Language: Английский

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Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(4), P. 2041 - 2076

Published: Feb. 23, 2024

Abstract In recent years, heightened interest surrounds the exploration of natural phenols as potential agents for cancer therapy, specifically by inducing ferroptosis, a unique form regulated cell death characterized iron‐dependent lipid peroxidation. This review delves into roles key phenols, flavonoids, phenolic acids, curcumin, and stilbenes, in modulating ferroptosis their underlying mechanisms. Emphasizing significance amino acid, lipid, iron metabolism, study elucidates diverse pathways through which these regulate ferroptosis. Notably, well‐known polyphenol, exhibits multifaceted interactions with cellular components involved regulation, providing distinctive therapeutic avenue. Stilbenes, another class, demonstrate promising influencing metabolism processes, contributing to ferroptotic death. Understanding intricate interplay between not only illuminates complex regulatory networks but also unveils avenues novel therapies. Exploring compounds inducers presents strategy targeted treatment, capitalizing on delicate balance article synthesizes current knowledge, aiming stimulate further research context ferroptosis‐mediated therapy.

Language: Английский

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NOX4 exacerbates Parkinson’s disease pathology by promoting neuronal ferroptosis and neuroinflammation

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(7), P. 2038 - 2052

Published: July 10, 2024

JOURNAL/nrgr/04.03/01300535-202507000-00026/figure1/v/2024-09-09T124005Z/r/image-tiff Parkinson’s disease is primarily caused by the loss of dopaminergic neurons in substantia nigra compacta. Ferroptosis, a novel form regulated cell death characterized iron accumulation and lipid peroxidation, plays vital role neurons. However, molecular mechanisms underlying ferroptosis have not yet been completely elucidated. NADPH oxidase 4 related to oxidative stress, however, whether it regulates neuronal remains unknown. The aim this study was determine involved ferroptosis, if so, what mechanism. We found that transcriptional regulator activating transcription factor 3 increased expression astrocytes an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced model. inhibition improved behavioral impairments observed model animals reduced Moreover, peroxidation animals. Mechanistically, we interacted with activated protein kinase C α prevent Furthermore, lowering astrocytic lipocalin-2 expression, neuroinflammation. These findings demonstrate promotes neuroinflammation, which contribute neuron death, suggesting possible therapeutic target for disease.

Language: Английский

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Ferroptosis: a new regulatory mechanism in neuropathic pain

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Sept. 22, 2023

Neuropathic pain (NP) is caused by damage to the somatosensory system. It a common progressive neurodegenerative disease that usually presents with clinical features such as spontaneous pain, touch-evoked nociceptive hyperalgesia, and sensory abnormalities. Due complexity of mechanism, NP often persists. In addition traditionally recognized mechanisms peripheral nerve central sensitization, excessive iron accumulation, oxidative stress, neuronal inflammation, lipid peroxidation are distinctive in pathophysiology. However, linking these pathological not fully understood. The pathogenesis greatly limits development therapeutic approaches for NP. Ferroptosis novel form cell death discovered recent years, which accompanied massive accumulation peroxidation. Ferroptosis-inducing factors can affect glutathione peroxidase directly or indirectly through different pathways, leading decreased antioxidant capacity reactive oxygen species (ROS) cells, ultimately death. has been shown ferroptosis closely related pathophysiological process many neurological disorders Possible involved changes intracellular ion levels, alteration glutamate excitability, onset stress. functional specific molecular during this still need be further explored. How intervene regulating cellular become hot issue etiological research treatment. review, we systematically summarize progress NP, provide reference understanding its propose new targets

Language: Английский

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Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis—A Systematic Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 334 - 334

Published: March 10, 2024

Ferroptosis is a recently discovered type of programmed cell death that mechanistically different from other types such as apoptosis, necroptosis, and autophagy. It characterized by the accumulation intracellular iron, overproduction reactive oxygen species, depletion glutathione, extensive lipid peroxidation lipids in membrane. was ferroptosis interconnected with many diseases, neurodegenerative ischemia/reperfusion injury, cancer, chronic kidney disease. Polyphenols, plant secondary metabolites known for bioactivities, are being extensively researched context their influence on which resulted great number publications showing need systematic review. In this review, an literature search performed. Databases (Scopus, Web Science, PubMed, ScienceDirect, Springer) were searched time span 2017 to November 2023, using keyword “ferroptosis” alone combination “flavonoid”, “phenolic acid”, “stilbene”, “coumarin”, “anthraquinone”, “chalcone”; after selection studies, we had 311 papers 143 phenolic compounds. total, 53 compounds showed ability induce ferroptosis, 110 able inhibit out those compounds, 20 both abilities depending model system. The most shikonin, curcumin, quercetin, resveratrol, baicalin. common modes action modulation Nrf2/GPX4 Nrf2/HO-1 axis iron metabolism.

Language: Английский

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New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6716 - 6716

Published: June 18, 2024

Neuropathic pain, which refers to pain caused by a lesion or disease of the somatosensory system, represents wide variety peripheral central disorders. Treating neuropathic is quite demanding, primarily because its intricate underlying etiological mechanisms. The nervous system relies on microglia maintain balance, as they are associated with serving primary immune responses in brain next cell communication. Ferroptosis, driven phospholipid peroxidation and regulated iron, vital mechanism death regulation. Neuroinflammation can be triggered ferroptosis microglia, contributes release inflammatory cytokines. Conversely, neuroinflammation induce iron accumulation resulting microglial ferroptosis. Accumulating evidence suggests that neuroinflammation, characterized glial activation substances, significantly exacerbates development pain. By inhibiting ferroptosis, it may possible prevent subsequently alleviate homopentameric α7 subtype neuronal nicotinic acetylcholine receptor (α7nAChR) has potential suppress activation, transitioning M1 an M2 phenotype, facilitating anti-inflammatory factors, ultimately reducing Recent years have witnessed growing recognition regulatory role α7nAChR could target for treating This review summarizes mechanisms related progress according recent research. Such exploration will help elucidate relationship between α7nAChR, provide new insights into management.

Language: Английский

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