Neuroscience Bulletin, Год журнала: 2025, Номер unknown
Опубликована: Янв. 7, 2025
Язык: Английский
Advanced Science, Год журнала: 2023, Номер 10(24)
Опубликована: Июнь 21, 2023
Emerging evidence suggests that ferroptosis, a unique regulated cell death modality is morphologically and mechanistically different from other forms of death, plays vital role in the pathophysiological process neurodegenerative diseases, strokes. Accumulating supports ferroptosis as critical factor diseases strokes, pharmacological inhibition therapeutic target for these diseases. In this review article, core mechanisms are overviewed roles strokes described. Finally, emerging findings treating through This demonstrates by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective treatments highlights potential promising avenue used to prevent article will shed light on developing novel regimens slow down progression future.
Язык: Английский
Процитировано
81
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Дек. 10, 2023
Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt
Язык: Английский
Процитировано
72
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
Процитировано
42
Chemical Reviews, Год журнала: 2025, Номер unknown
Опубликована: Фев. 14, 2025
Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.
Язык: Английский
Процитировано
4
Heliyon, Год журнала: 2023, Номер 9(10), С. e20163 - e20163
Опубликована: Сен. 21, 2023
Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis chondrocytes OA unknown. This study aimed to investigate protective potential mechanism curcumin induced by erastin, inducer. CCK-8 assays were used assess viability mouse primary treated 3.33 μM erastin alone or combination different doses curcumin. Various parameters detected, including LDH, SOD, GSH-PX, MDA, ROS Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, FTH1, examined using immunofluorescence western blotting. Nrf2 was knocked down siRNA explore molecular through which protects from erastin-induced ferroptosis. In model knee intracavity injection 10 μL (5 mg/mL), HE staining, Safranin O-Fast Green immunohistochemistry employed evaluate articular cartilage injury. results demonstrated that significantly suppressed expression FTH1 while upregulating levels ROS, TFR1 chondrocytes. Moreover, chondrocyte production reversed Additionally, upregulated level gene protein. Silencing animal experiments, silencing counteracted impact damage tissue vivo, leading significant inhibition progression. Taken together, these findings suggest can inhibit activating signaling pathway, providing further insight into regulatory supporting therapeutic use treatment.
Язык: Английский
Процитировано
25
Molecular Neurobiology, Год журнала: 2023, Номер 61(3), С. 1507 - 1526
Опубликована: Сен. 19, 2023
Язык: Английский
Процитировано
24
Antioxidants, Год журнала: 2024, Номер 13(9), С. 1109 - 1109
Опубликована: Сен. 13, 2024
Oxidative stress is the result of imbalance between reactive oxygen and nitrogen species (RONS), which are produced by several endogenous exogenous processes, antioxidant defenses consisting molecules that protect biological systems from free radical toxicity. a major factor in aging process, contributing to accumulation cellular damage over time. biomolecules, leads DNA alterations, lipid peroxidation, protein oxidation, mitochondrial dysfunction resulting senescence, immune system tissue dysfunctions, increased susceptibility age-related pathologies, such as inflammatory disorders, cardiovascular neurodegenerative diseases, diabetes, cancer. stress-driven mutations, or methylation histone modification, alter gene expression, key determinants tumor initiation, angiogenesis, metastasis, therapy resistance. Accumulation genetic epigenetic damage, oxidative contributes, eventually unrestrained cell proliferation, inhibition differentiation, evasion death, providing favorable conditions for tumorigenesis. Colorectal, breast, lung, prostate, skin cancers most frequent aging-associated malignancies, implicated their pathogenesis behavior. Our aim shed light on molecular mechanisms link stress, aging, cancers, highlighting impact both RONS antioxidants, provided diet exercise, immunity, development an antitumor response. The dual role ROS physiological regulators signaling responsible well its use anti-tumor therapeutic purposes, will also be discussed. Managing crucial promoting healthy reducing risk tumors.
Язык: Английский
Процитировано
15
Redox Biology, Год журнала: 2024, Номер 71, С. 103119 - 103119
Опубликована: Март 11, 2024
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the build-up of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Ferroptosis, an iron (Fe)-dependent form cell death plays significant role in multifaceted AD pathogenesis through generation reactive oxygen species (ROS), mitochondrial damage, lipid peroxidation, reduction glutathione peroxidase 4 (GPX4) enzyme activity levels. Aberrant liquid-liquid phase separation (LLPS) tau drives growth maturation NFTs contributing to pathogenesis. In this study, we strategically combined structural functional properties gallic acid (GA) cyclic dipeptides (CDPs) synthesize hybrid molecules that effectively target both ferroptosis toxicity AD. This innovative approach marks paradigm shift from conventional therapeutic strategies. first report synthetic small molecule (GCTR) combats ferroptosis, simultaneously restoring enzymatic enhancing cellular levels its master regulator, GPX4. Further, GCTR disrupts Fe3+-induced LLPS tau, aids attenuation abnormal fibrillization. The synergistic action combating toxicity, bolstered GPX4 enhancement modulation LLPS, holds promise for development molecule-based novel therapeutics
Язык: Английский
Процитировано
14
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116453 - 116453
Опубликована: Март 20, 2024
Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is heterogenous complex clinical syndrome caused by the dysfunctional response host to infection. This leads excess mortality and morbidity worldwide. Despite relevance with high incidence, there lack understanding for its both acute/chronic pathogenesis therapeutic management. A better molecular mechanisms behind SAE may provide tools enhance efficacy. Mounting evidence indicates that some types non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, autophagy, contribute SAE. Targeting these RCD meaningful targets future treatments against review summarizes core mechanism which We focus on emerging compounds can inhibit delineate their beneficial pharmacological effects Within this we suggest inhibition serve potential strategy
Язык: Английский
Процитировано
12
Advanced Science, Год журнала: 2024, Номер unknown
Опубликована: Окт. 28, 2024
Abstract Myocardial ischemia‐reperfusion injury (MIRI) significantly worsens the outcomes of patients with cardiovascular diseases. Dexmedetomidine (Dex) is recognized for its cardioprotective properties, but related mechanisms, especially regarding metabolic reprogramming, have not been fully clarified. A total 60 heart valve disease are randomly assigned to Dex or control group. Blood samples collected analyze cardiac biomarkers and metabolomics. In vivo vitro rat models MIRI utilized assess effects on function, lactate production, mitochondrial function. It found that postoperative CK‐MB cTNT levels lower in Metabolomics reveals regulates reprogramming reduces level. Dex‐treated rats, myocardial infarction area reduced, contractility improved. inhibits glycolysis, lactate, improves function following MIRI. Lactylation proteomics identifies lactylation Malate Dehydrogenase 2（MDH2), thus alleviating injury. Further studies reveal MDH2 induces ferroptosis, leading by impairing Mechanistic analyses upregulates Nuclear Receptor Subfamily 3 Group C Member 1（NR3C1) phosphorylation, downregulates Pyruvate Kinase 4 (PDK4), production lactylation. These findings provide new therapeutic targets mechanisms treatment
Язык: Английский
Процитировано
11