Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217696 - 217696
Published: April 1, 2025
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
56
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Jan. 2, 2025
Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing
Language: Английский
Citations
2
Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107063 - 107063
Published: Jan. 11, 2024
Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating signaling pathways to defend the host. Recent studies have revealed additional regulatory functions STING beyond its immune-related activities, including regulation cellular metabolism, DNA repair, senescence, autophagy various cell deaths. These findings highlight broader implications in physiology role immunity. Currently, approximately 10 agonists entered clinical stage. Unlike inhibitors, which maximum inhibition limit, potential infinite amplification. complex process that requires precise ensure balanced responses prevent detrimental autoinflammation. research on structural mechanism autoinhibition negative by adaptor protein 1 (AP-1) provides valuable insights into different effects under physiological pathological conditions, offering new perspective developing drugs. Herein, we present comprehensive overview molecular mechanisms regulation, along with updated details mechanisms. We discuss these regulations diseases, emphasizing importance feasibility targeting immunity-dependent or immunity-independent STING. Moreover, current trend drug development key points research, basic translational related
Language: Английский
Citations
14
International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(7), P. 2507 - 2531
Published: Jan. 1, 2024
Neuropeptide substance P (SP) belongs to a family of bioactive peptides and regulates many human diseases. This study aims investigate the role underlying mechanisms SP in colitis. Here, activated SP-positive neurons increased expression were observed dextran sodium sulfate (DSS)-induced colitis lesions mice. Administration exogenous efficiently ameliorated clinical symptoms, impaired intestinal barrier function, inflammatory response. Mechanistically, protected mitochondria from damage caused by DSS or TNF-α exposure, preventing mitochondrial DNA (mtDNA) leakage into cytoplasm, thereby inhibiting cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway. can also directly prevent STING phosphorylation through neurokinin-1 receptor (NK1R), activation TBK1-IRF3 signaling Further studies revealed that alleviated TNF-α-induced ferroptosis process, which was associated with repressing cGAS-STING Notably, we identified NK1R inhibition reversed effects on inflammation via Collectively, unveil attenuates suppressing mtDNA-cGAS-STING acting pathway, contributing improving an NK1R-dependent manner. These findings provide novel mechanism regulating ulcerative (UC) disease.
Language: Английский
Citations
11
Redox Biology, Journal Year: 2024, Volume and Issue: 77, P. 103360 - 103360
Published: Sept. 20, 2024
Acute kidney injury (AKI) is primarily caused by renal ischemia-reperfusion (IRI), which one of the most prevalent triggers. Currently, preventive and therapeutic measures remain limited. Ferroptosis plays a significant role in pathophysiological process IRI-induced AKI considered key target for improving its outcomes. Silibinin, polyphenolic flavonoid, possesses diverse pharmacological properties widely used as an effective agent liver diseases. Recent studies have reported that silibinin may improves diseases, though underlying mechanism unclear. In this study, we investigated whether protects against explored action. Our findings indicated pretreatment with alleviated dysfunction, pathological damage, inflammation IRI-AKI mice. Furthermore, results demonstrated inhibited ferroptosis both vivo vitro. Proteome microarrays were to identify silibinin's target, our revealed binds FTH1. This binding affinity was confirmed through molecular docking, SPRi, CETSA, DARTS. Additionally, co-IP assays disrupted NCOA4-FTH1 interaction, inhibiting ferritinophagy. Finally, inhibitory effects on reversed knocking down FTH1 conclusion, study shows effectively alleviates targeting reduce ferroptosis, suggesting could be developed potential managing treating AKI.
Language: Английский
Citations
11
Advanced Science, Journal Year: 2024, Volume and Issue: 11(33)
Published: July 4, 2024
Acute kidney injury (AKI) signifies a sudden and prolonged decline in function characterized by tubular cell death interstitial inflammation. Small nucleolar RNAs (snoRNAs) play pivotal roles oxidative stress inflammation, may an important role the AKI process, which remains elusive. elevated expression of Snord3a is revealed renal tubules response to demonstrates that deficiency alleviates mouse models. Notably, exhibits mitigating effect on stimulator interferon genes (STING)-associated ferroptosis phenotypes progression injury. Mechanistically, shown regulate STING signaling axis via promoting gene transcription; administration antisense oligonucleotides establishes significant therapeutic advantage Together, findings elucidate transcription regulation mechanism crucial Snord3a-STING during AKI, underscoring as potential prognostic target for AKI.
Language: Английский
Citations
8
Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 7, 2025
Language: Английский
Citations
1
Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 10, 2025
Language: Английский
Citations
1
Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 399, P. 111152 - 111152
Published: July 16, 2024
Language: Английский
Citations
7
Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 714 - 714
Published: June 12, 2024
Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality life. Ferroptosis, an iron-dependent form programmed cell death, has been implicated in the pathogenesis cisplatin-induced ototoxicity. Here, we investigated effects nuciferine, natural active ingredient isolated from lotus species, on ferroptosis cochlear hair cells. Firstly, our results demonstrated that nuciferine protect cells against RSL3-induced damage. Secondly, treatment reduced ferrous iron (Fe2+) overload via inhibiting NCOA4-mediated ferritinophagy. Inhibition ferritinophagy by knocking down Ncoa4 alleviated Importantly, mitigated loss damage to ribbon synapse, improved mouse function acute model. Our findings highlight role ototoxicity provide evidence promising protective agent loss.
Language: Английский
Citations
6