The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 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.

Язык: Английский

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Srs11‐92, a ferrostatin‐1 analog, improves oxidative stress and neuroinflammation via Nrf2 signal following cerebral ischemia/reperfusion injury

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(6), С. 1667 - 1677

Опубликована: Фев. 27, 2023

Ferroptosis is increasingly becoming to be considered as an important mechanism of pathological cell death during stroke, and specific exogenous ferroptosis inhibitors have the ability reverse cerebral ischemia/reperfusion injury. However, research on Srs11-92 (AA9), a ferrostatin-1 (Fer-1) analog, in preclinical studies limited.In middle artery occlusion-reperfusion (MCAO/R) mice model or oxygen-glucose deprivation/reperfusion (OGD/R) model, Fer-1, AA9, and/or ML385 were administered, brain infarct size, neurological deficits, neuronal damage, oxidative stress, neuroinflammation determined after vitro vivo.Fer-1 AA9 improved deficits MCAO/R, inhibited overloaded iron deposition, ROS accumulation, response: it also increased expression GPx4, Nrf2, HO-1 suppressed HMGB1 NF-κB p65 epicenter injured hippocampal formation. Nrf2 inhibitor reversed neuroprotective effect including stress neuroinflammation. In showed that relieved OGD/R-induced via pathway, which was impaired by primary neurons.The findings imply Fer-1 analog may suitable for further translational protection damage signal pathway-mediated stroke others diseases.

Язык: Английский

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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 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

Язык: Английский

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The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Antioxidants, Год журнала: 2024, Номер 13(4), С. 395 - 395

Опубликована: Март 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Язык: Английский

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Progress of Ferroptosis in Ischemic Stroke and Therapeutic Targets

Cellular and Molecular Neurobiology, Год журнала: 2024, Номер 44(1)

Опубликована: Фев. 23, 2024

Ferroptosis is an iron-dependent form of programmed cell death (PCD) and ischemic stroke (IS) has been confirmed to be closely related ferroptosis. The mechanisms ferroptosis were summarized into three interrelated aspects: iron metabolism, lipid peroxide as well glutathione amino acid metabolism. What's more, the causal relationship between IS elucidated by several processes. disruption blood-brain barrier, release excitatory acids, inflammatory response after all lead disorder metabolism antioxidant system. Based on these statements, we reviewed reported effects compounds drugs treating modulating key molecules in Through detailed analysis roles molecules, have also more clearly demonstrated essential effect occurrence so provide new targets ideas for therapeutic IS.

Язык: Английский

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Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 891 - 891

Опубликована: Янв. 10, 2024

Stroke is a major cause of death and disability worldwide. Endovascular thrombectomy has been impactful in decreasing mortality. However, many clinical results continue to show suboptimal functional outcomes despite high recanalization rates. This gap symptomatic improvement suggests need for adjunctive therapies post-thrombectomy care. With greater insight into ischemia-reperfusion injury, recent preclinical testing neuroprotective agents shifted towards preventing oxidative stress through upregulation antioxidants downstream effectors, with positive results. Advances multiple therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapamil, butylphthalide, edaravone, nelonemdaz, ApTOLL, regional hypothermia, remote ischemic conditioning, normobaric oxygen, especially nuclear factor erythroid 2-related 2, have promising evidence improving stroke Sedation blood pressure management endovascular also play crucial roles improved outcomes. A hand-in-hand approach both therapy neuroprotection may be the key targeting due stroke.

Язык: Английский

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WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury

International Journal of Surgery, Год журнала: 2024, Номер 110(9), С. 5396 - 5408

Опубликована: Июнь 14, 2024

Background Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, authors explored epigenetic methylation RNA-mediated NLRP3 inflammasome activation Methods Neurological dysfunction, histopathology, associated molecules were examined in conditional knockout (CKO) WTAP [flox/flox, Camk2a-cre] , flox/flox pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons used vitro to further explore molecular mechanisms action WTAP/YTHDF1 following neural damage. Results The found that m6A levels upregulated at early stage TBI, deletion did not affect function but promoted functional recovery Conditional suppressed neuroinflammation TBI phase: could directly act on mRNA, regulate mRNA level, promote expression neuronal injury. Further investigation YTH domain YTHDF1 bind protein expression. mutation or silencing improved injury, inhibited Caspase-1 activation, decreased IL-1β levels. This effect was mediated via suppression translation, which also reversed stimulative overexpression inflammation. Conclusions Our results indicate participates damage by translation m6A-YTHDF1-dependent manner WTAP/m6A/YTHDF1 downregulation therapeutics viable promising approach preserving can provide support targeted drug development.

Язык: Английский

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Ferroptosis in organ ischemia–reperfusion injuries: recent advancements and strategies

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер unknown

Опубликована: Март 31, 2024

Язык: Английский

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Targeting ferroptosis in neuroimmune and neurodegenerative disorders for the development of novel therapeutics

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116777 - 116777

Опубликована: Май 24, 2024

Neuroimmune and neurodegenerative ailments impose a substantial societal burden. disorders involve the intricate regulatory interactions between immune system central nervous system. Prominent examples of neuroimmune encompass multiple sclerosis neuromyelitis optica. Neurodegenerative diseases result from neuronal degeneration or demyelination in brain spinal cord, such as Alzheimer's disease, Parkinson's Huntington's amyotrophic lateral sclerosis. The precise underlying pathogenesis these conditions remains incompletely understood. Ferroptosis, programmed form cell death characterised by lipid peroxidation iron overload, plays pivotal role diseases. In this review, we provide detailed overview ferroptosis, its mechanisms, pathways, regulation during progression Furthermore, summarise impact ferroptosis on neuroimmune-related cells (T cells, B neutrophils, macrophages) neural (glial neurons). Finally, explore potential therapeutic implications inhibitors diverse

Язык: Английский

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N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis

European Journal of Pharmacology, Год журнала: 2024, Номер 972, С. 176553 - 176553

Опубликована: Апрель 2, 2024

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process ischemic stroke is complex, and it crucial to elucidate its molecular mechanisms explore potential protective drugs. Ferroptosis, newly recognized form programmed cell death distinct from necrosis, apoptosis, autophagy, closely associated with pathophysiology stroke. N6022, selective inhibitor S-nitrosoglutathione reductase (GSNOR), "first-in-class" drug for asthma therapeutic applications. However, remains unclear whether N6022 exerts effects in stroke, precise action are unknown. This study aimed investigate mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) model middle artery occlusion/reperfusion (MCAO/R) mouse mimic I/R injury. Our data, both vitro vivo, demonstrated that effectively protected against I/R-induced brain damage neurological deficits mice, as well OGD/R-induced BV2 damage. Mechanistically, promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity SLC7A11-GPX4 system. Furthermore, interfered interaction GSNOR GSTP1, thereby boosting GSTP1 attenuating ferroptosis. These findings provide novel insights, showing attenuates microglial induced through promotion translocation inhibition GSNOR/GSTP1 axis.

Язык: Английский

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