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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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: March 29, 2024

Abstract To date, several molecules have been found to facilitate iron influx, while the types of influx channels remain be elucidated. Here, Piezo1 channel was identified as a key transporter in response mechanical stress. Piezo1-mediated overload disturbed metabolism and exaggerated ferroptosis nucleus pulposus cells (NPCs). Importantly, Piezo1-induced independent transferrin receptor (TFRC), well-recognized gatekeeper. Furthermore, pharmacological inactivation profoundly reduced accumulation, alleviated mitochondrial ROS, suppressed ferroptotic alterations stimulation Moreover, conditional knockout ( Col2a1-CreERT flox/flox ) attenuated injury-induced intervertebral disc degeneration (IVDD). Notably, protective effect deficiency IVDD dampened Piezo1/Gpx4 double (cDKO) mice /Gpx4 ). These findings suggest that is potential determinant indicating Piezo1-iron-ferroptosis axis might shed light on treatment stress-induced diseases.

Language: Английский

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Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract Objective Human immunodeficiency virus (HIV)-infected individuals who abuse methamphetamine (METH) exhibit more severe neurotoxicity and cognitive impairment. Pyroptosis, a programmed cell death pathway mediated by the inflammasome, has been implicated in various neurological diseases. This study aimed to elucidate role of AIM2 inflammasome METH- HIV-1 Tat-induced pyroptosis human brain tissue vitro models. Methods Postmortem from HIV-infected with history METH was analyzed for markers components using immunohistochemistry, immunofluorescence, Western blotting. BV2 microglial cells were lentivirally transduced knockdown expression. DNA damage assessed blotting comet assay. Expression pyroptosis-related proteins evaluated electron microscopy, blotting, immunofluorescence. Cell viability measured CCK8 Results Elevated levels observed users. Tat synergistically induced time- concentration-dependent manner, accompanied activation inflammasome. Knockdown significantly reduced expression proteins. Conclusion induce activating through dsDNA damage. These findings suggest that targeting may be promising therapeutic strategy HIV-associated neurocognitive disorder (HAND). Graphical abstract

Language: Английский

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TRIM28 Fosters Microglia Ferroptosis via Autophagy Modulation to Enhance Neuropathic Pain and Neuroinflammation

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(11), P. 9459 - 9477

Published: April 22, 2024

Language: Английский

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Ferritin: Significance in viral infections

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(2)

Published: March 1, 2024

As an indispensable trace element, iron is essential for many biological processes. Increasing evidence has shown that virus infection can perturb metabolism and play a role in the occurrence development of viral infection-related diseases. Ferritin plays crucial maintaining body's homoeostasis. It important protein to stabilise balance cells. 24-mer hollow storage composed two subunits: ferritin heavy chain light chain. was reported not only intra-cellular protein, but also pathogenic mediator enhances inflammatory process stimulates further pathway, which key member vicious cycle perpetuate. exerts immuno-suppressive pro-inflammatory functions during infection. In this review, we describe detail basic information first section, including its structural features, regulation ferritin. second part, focus on diseases molecular mechanisms by regulates The last section briefly outlines potential antiviral therapy. Given importance infection, understanding helps us understand relationship between metabolic dysfunction provides new direction therapeutic drugs.

Language: Английский

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The Regulation of Ferroptosis by Noncoding RNAs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13336 - 13336

Published: Aug. 28, 2023

As a novel form of regulated cell death, ferroptosis is characterized by intracellular iron and lipid peroxide accumulation, which different from other death forms morphologically, biochemically, immunologically. Ferroptosis metabolism, antioxidant defense systems as well various transcription factors related signal pathways. Emerging evidence has highlighted that associated with many physiological pathological processes, including cancer, neurodegeneration diseases, cardiovascular ischemia/reperfusion injury. Noncoding RNAs are group functional RNA molecules not translated into proteins, can regulate gene expression in manners. An increasing number studies have shown noncoding RNAs, especially miRNAs, lncRNAs, circRNAs, interfere the progression modulating ferroptosis-related genes or proteins directly indirectly. In this review, we summarize basic mechanisms regulations focus on recent mechanism for types ncRNAs to conditions, will deepen our understanding regulation provide new insights employing ferroptosis-associated therapeutic strategies.

Language: Английский

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The interplay of miRNAs and ferroptosis in diseases related to iron overload

APOPTOSIS, Journal Year: 2023, Volume and Issue: 29(1-2), P. 45 - 65

Published: Sept. 27, 2023

Language: Английский

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Mitochondria-mediated ferroptosis contributes to the inflammatory responses of bovine viral diarrhea virus (BVDV) in vitro

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(2)

Published: Jan. 16, 2024

Bovine viral diarrhea virus (BVDV) threatens a wide range of domestic and wild cattle population worldwide. BVDV causes great economic loss in industry through its immunosuppression persistent infection. Despite extensive research, the mechanism underlying pathogenesis remains elusive. Our data provide first direct evidence that mitochondria-mediated ferroptosis mitophagy are involved inflammatory responses both biotypes BVDV-infected cells. Importantly, we demonstrate different degrees injury mitochondria may attribute to pathways induced by BVDV. Overall, our findings uncover interaction between infection ferroptosis, which shed novel light on physiological impacts infection, promising therapeutic strategy treat this important infectious disease with worldwide distribution.

Language: Английский

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EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis

Viruses, Journal Year: 2024, Volume and Issue: 16(5), P. 693 - 693

Published: April 27, 2024

EcoHIV is a chimeric HIV that replicates in mice CD4+ T cells, macrophages, and microglia (but not neurons), causing lasting neurocognitive impairment resembling disease people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures investigate the indirect effects of infection on neuronal integrity. We used two clones encoding EGFP bone marrow-derived macrophages (BMM), mixed or enriched glial cells from wild-type strains test replication efficiency, identity productively infected apoptosis replicated efficiently BMM. In cell cultures, targeted but did cause apoptosis. Instead, productive activated them impaired synaptophysin expression, dendritic density, axonal structure neurons. structural changes during were prevented by culture an antiretroviral. murine largely responsible for aspects dysfunction relevant cognitive These provide tool further neuropathogenesis its control.

Language: Английский

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Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116761 - 116761

Published: May 23, 2024

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form regulated by excessive lipid peroxidation, been shown to drive development multiple CVDs. This review provides insights into evolution concept similarities and differences with traditional modes programmed (e.g., apoptosis, autophagy, necrosis), as well core mechanisms ferroptosis (including cystine/glutamate transporter blockade, imbalance iron metabolism, peroxidation). In addition, it not only a detailed role its potential widely studied CVDs such coronary atherosclerotic heart disease, myocardial infarction, ischemia/reperfusion injury, failure, cardiomyopathy, aortic aneurysm but also overview phenomenon perspectives lesser-addressed cardiac valvulopathy, pulmonary hypertension, sickle disease. article aims integrate this knowledge provide comprehensive view wide range progress strategies field.

Language: Английский

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