Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(4), P. 815 - 833
Published: Jan. 3, 2024
Language: Английский
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
Citations
50
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1314 - 1314
Published: Jan. 21, 2024
Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from substrates oxygen produce adenosine triphosphate. also regulate proliferation, metastasis, and deterioration. The flow in mitochondrial respiratory chain generates reactive species (ROS), which harmful cells at high levels. stress caused by ROS accumulation has been associated with an increased risk cancer, cardiovascular liver diseases. Glutathione (GSH) is abundant cellular antioxidant that primarily synthesized cytoplasm delivered mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within A long-term imbalance ratio mGSH can cause dysfunction, apoptosis, necroptosis, ferroptosis, may lead disease. This study aimed review physiological functions, anabolism, variations organ tissue accumulation, delivery GSH mitochondria relationships between levels, GSH/GSH disulfide (GSSG) ratio, programmed death, ferroptosis. We discuss diseases deficiency related therapeutics.
Language: Английский
Citations
48
Redox Biology, Journal Year: 2024, Volume and Issue: 74, P. 103194 - 103194
Published: May 16, 2024
Elevated lactate levels are a significant biomarker of sepsis and positively associated with sepsis-related mortality. Sepsis-associated lung injury (ALI) is leading cause poor prognosis in clinical patients. However, the underlying mechanisms lactate's involvement sepsis-associated ALI remain unclear. In this study, we demonstrate that regulates N6-methyladenosine (m6A) modification by facilitating p300-mediated H3K18la binding to METTL3 promoter site. The METTL3-mediated m6A enriched ACSL4, its mRNA stability regulated through YTHDC1-dependent pathway. Furthermore, short-term stimulation upregulates which promotes mitochondria-associated ferroptosis. Inhibition knockdown or targeted inhibition effectively suppresses septic hyper-lactate-induced ferroptosis alveolar epithelial cells mitigates mice. Our findings suggest induces via GPR81/H3K18la/METTL3/ACSL4 axis during ALI. These results reveal histone lactylation-driven mechanism inducing modification. Targeting represents promising therapeutic strategy for patients
Language: Английский
Citations
32
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: June 6, 2024
Abstract The adaptability of glioblastoma (GBM) cells, encouraged by complex interactions with the tumour microenvironment (TME), currently renders GBM an incurable cancer. Despite intensive research, many clinical trials, patients rely on standard treatments including surgery followed radiation and chemotherapy, which have been observed to induce a more aggressive phenotype in recurrent tumours. This failure improve is undoubtedly result insufficient models fail incorporate components human brain TME. Research has increasingly uncovered mechanisms tumour-TME that correlate worsened patient prognoses, tumour-associated astrocyte mitochondrial transfer, neuronal circuit remodelling immunosuppression. hijacked TME highly implicated driving therapy resistance, further alterations within resulting from exposure inducing increased growth invasion. Recent developments improving organoid models, aspects TME, are paving exciting future for research drug development GBM, hopes survival growing closer. review focuses GBMs their effect pathology treatment efficiency, look at challenges face sufficiently recapitulating this adaptive
Language: Английский
Citations
22
Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103158 - 103158
Published: April 12, 2024
Exposure to PM2.5 is correlated with cardiac remodeling, of which hypertrophy one the main clinical manifestations. Ferroptosis plays an important role in hypertrophy. However, potential mechanism PM2.5-induced through ferroptosis remains unclear. This study aimed explore molecular caused by and intervention MitoQ involved this process. The results showed that could induce dysfunction mice. Meanwhile, characteristics were observed, such as iron homeostasis imbalance, lipid peroxidation, mitochondrial damage abnormal expression key molecules. treatment effectively mitigate these alternations. After treating human cardiomyocyte AC16 PM2.5, activator (Erastin) inhibitor (Fer-1), it was found promote ferritinophagy lead well accumulation intracellular labile iron. Subsequently, mitophagy activated provided additional source iron, enhancing sensitivity cells ferroptosis. Furthermore, Fer-1 alleviated cytotoxicity overload cytoplasm mitochondria cells. It worth noting during process ferroptosis, metabolism mediated activation a temporal order. In addition, NCOA4 knockdown reversed imbalance peroxidation thereby alleviating summary, our imbalance-mediated crosstalk played
Language: Английский
Citations
17
Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)
Published: Feb. 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.
Language: Английский
Citations
15
Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 298 - 298
Published: Feb. 28, 2024
Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.
Language: Английский
Citations
15
Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)
Published: May 30, 2024
Abstract Ferroptosis represents a form of programmed cell death that is propelled by iron-dependent lipid peroxidation, thereby being distinguished the prominent features iron accumulation and peroxidation. has been implicated in numerous physiological pathological phenomena, with mounting indications it holds significant implications for cancer other medical conditions. On one side, demonstrates anti-cancer properties triggering ferroptosis within malignant cells, on hand, damages normal cells causing diseases. Therefore, this paper, we propose to review paradoxical regulation tumors First, introduce development history, concept mechanism ferroptosis. The second part focuses methods inducing tumors. third section emphasizes utilization different conditions strategies inhibit fourth elucidates key contradictions control Finally, potential research avenues associated domains are suggested.
Language: Английский
Citations
15
Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(5), P. 2961 - 2986
Published: Aug. 10, 2024
Language: Английский
Citations
13
Life Sciences, Journal Year: 2024, Volume and Issue: 343, P. 122555 - 122555
Published: March 7, 2024
Language: Английский
Citations
11