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

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

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E3 ligases and DUBs target ferroptosis: A potential therapeutic strategy for neurodegenerative diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116753 - 116753

Published: May 17, 2024

Ferroptosis is a form of cell death mediated by iron and lipid peroxidation (LPO). Recent studies have provided compelling evidence to support the involvement ferroptosis in pathogenesis various neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's (PD). Therefore, understanding mechanisms that regulate NDDs may improve management. regulated multiple mechanisms, different degradation pathways, including autophagy ubiquitinproteasome system (UPS), orchestrate complex response directly or indirectly regulating accumulation peroxidation. Ubiquitination plays crucial role protein posttranslational modification driving ferroptosis. Notably, E3 ubiquitin ligases (E3s) deubiquitinating enzymes (DUBs) are key system, their dysregulation closely linked progression NDDs. A growing body highlights sensitivity. However, reports on interaction between signaling scarce. In this review, we first provide brief overview biological processes roles UPS, summarize core molecular potential functions ferroptosis, explore pathophysiological relevance therapeutic implications addition, reviewing E3s DUBs aims new insights strategies for treatment These include E3- DUB-targeted drugs inhibitors, which can be used prevent ameliorate

Language: Английский

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Integrated Analysis and Validation of Ferroptosis-Related Genes Associated with Ischemia/Reperfusion Injury in Lung Transplantation

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 251 - 270

Published: Jan. 1, 2025

Background: Lung transplantation is the only effective therapeutic option for patients with end-stage lung disease. However, ischemia/reperfusion injury (IRI) during a leading cause of primary graft dysfunction (PGD). Ferroptosis, form iron-dependent cell death driven by lipid peroxidation, has been implicated in IRI across various organs. This study aims to explore role ferroptosis transplantation-related and identify its potential molecular mechanisms through bioinformatics analysis. Methods: Transcriptome data from transplant were obtained Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (FRGs) identified analyzing gene expression profiles before after reperfusion. Weighted co-expression network analysis (WGCNA) was used module genes, overlapping further analyzed using two machine learning algorithms. The CIBERSORT algorithm applied assess immune infiltration, while Mendelian randomization (MR) investigate causal relationships between candidate PGD. Finally, Consensus clustering based on FRGs performed subtypes. Results: We four associated reperfusion: tumor necrosis factor alpha-induced protein 3 (TNFAIP3), C-X-C motif chemokine ligand 2 (CXCL2), neural precursor developmentally down-regulated 4-like (NEDD4L), sestrin (SESN2). These closely infiltration. MR suggested that SESN2 might play protective against Additionally, consensus revealed distinct infiltration patterns subtypes, providing insights personalized approaches (LIRI). Conclusion: highlights TNFAIP3, CXCL2, NEDD4L, as LIRI, potentially protecting findings offer promising targets preventing LIRI improving outcomes transplantation. Keywords: injury, ferroptosis, biomarkers,

Language: Английский

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The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

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Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 4, 2025

Abstract Background Huntington's disease (HD) could cause progressive motor deficits, psychiatric symptoms, and cognitive impairment. With the increasing use of pharmacotherapies theoretically target neurotransmitters, incidence HD is still not decreasing. However, molecular pathogenesis have been illuminate. It momentous to further examine HD. Methods The next generation sequencing dataset GSE105041 was downloaded from Gene Expression Omnibus (GEO) database. Using DESeq2 in R bioconductor package screen differentially expressed genes (DEGs) between samples normal control samples. ontology (GO) term REACTOME pathway enrichment were performed on DEGs. Meanwhile, using Integrated Interactions Database (IID) database Cytoscape software construct protein–protein interaction (PPI) network module analysis, identify hub with highest value node degree, betweenness, stress closeness scores. miRNA-hub gene regulatory TF-hub constructed analyzed. Receiver operating characteristic curves analysis for diagnostic genes. Results We identified 958 DEGs, consisting 479 up regulated DEGs down GO terms analyses by g:Profiler online results revealed that mainly enriched multicellular organismal process, developmental signaling GPCR MHC class II antigen presentation. Network Analyzer plugin PPI network, LRRK2, MTUS2, HOXA1, IL7R, ERBB3, EGFR, TEX101, WDR76, NEDD4L COMT selected as Hsa-mir-1292-5p, hsa-mir-4521, ESRRB SREBF1 are potential biomarkers predicted be associated Conclusion This study investigated key pathways interactions its complications, which might help reveal correlation complications. current investigation captured prediction, follow-up biological experiments enforced validation.

Language: Английский

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Emerging importance of m6A modification in liver cancer and its potential therapeutic role

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189299 - 189299

Published: March 1, 2025

Language: Английский

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Research progress of ferroptosis pathway and its related molecular ubiquitination modification in liver cancer

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 21, 2025

As a new type of programmed cell death, ferroptosis is characterized by iron metabolism disorder and reactive oxygen species (ROS) accumulation, involved in regulating the occurrence development cancer cells. Especially field liver treatment, shows great potential because it can induce tumor death. Ubiquitination process protein post-translational modification, which affect stability proteins regulate progress ferroptosis. This article reviews research ubiquitination modification molecules related to pathway regulation cancer, providing strategy for treatment cancer.

Language: Английский

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METTL3-dependent m ⁶ A modification of SNAP29 induces “autophagy-mitochondrial crisis” in the ischemic microenvironment after soft tissue transplantation

Autophagy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 24

Published: May 8, 2025

Necrosis at the ischemic distal end of flap transplants increases patients' pain and economic burden. Reactive oxygen species (ROS) mitochondrial damage are crucial in regulating parthanatos, but mechanisms linking disrupted macroautophagic/autophagic flux to parthanatos flaps remain unclear. The results western blotting, immunofluorescence staining, a proteomic analysis revealed that autophagic protein SNAP29 was deficient flaps, resulting flux, increased ROS-induced aggravated necrosis. use AAV vector restore vivo mitigated disruption parthanatos. Additionally, quantification total m6A level RIP-qPCR, MeRIP-qPCR, RNA stability assessments were performed determine differential Snap29 mRNA methylation levels flaps. Various vitro tests conducted verify ability METTL3-mediated promote depletion disrupt flux. Finally, we concluded restoring by inhibiting METTL3 YTHDF2 reversed "autophagy-mitochondrial crisis", defined for first time as damage, leakage, occurrence reversal this crisis ultimately promoted survival flaps.Abbreviations: = adeno-associated virus; ACTA2/α-SMA actin alpha 2, smooth muscle, aorta; AIFM/AIF apoptosis-inducing factor, mitochondrion-associated; ALKBH5 alkB homolog, demythelase; Baf A1 bafilomycin A1; CQ chloroquine; DHE dihydroethidium; ECs endothelial cells; F-CHP 5-FAM-conjugated collagen-hybridizing peptide; GO gene ontology; HUVECs human umbilical vein KEGG Kyoto Encyclopedia Genes Genomes; LC-MS/MS liquid chromatography-tandem mass spectrometry; LDBF laser doppler blood flow; N6-methyladenosine; MAP1LC3/LC3 microtubule-associated 1 light chain 3; MeRIP methylated immunoprecipitation; methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit; NAC N-acetylcysteine; OGD glucose deprivation; PAR poly (ADP-ribose); PARP1 (ADP-ribose) polymerase family, member 1; PECAM1/CD31 platelet/endothelial cell adhesion molecule ROS reactive species; RT-qPCR reverse transcription quantitative reaction; RIP synaptosomal-associated 29; SNARE soluble N-ethylmaleimide-sensitive factor attachment receptor; SQSTM1 sequestosome SRAMP sequence-based adenosine site predicting; STX17 syntaxin 17; TMT tandem tag; TUNEL terminal deoxynucleotidyl transferase dUTP nick labeling; VAMP8 vesicle-associated membrane 8; WTAP WT1 associating protein; YTH N6-methyladenosine binding 2; 3' UTR 3'-untranslated region.

Language: Английский

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Luteolin protects mouse hippocampal neuronal cells against isoflurane-induced neurotoxicity through miR-214/PTEN/Akt pathway

NeuroToxicology, Journal Year: 2024, Volume and Issue: 103, P. 310 - 319

Published: July 1, 2024

Language: Английский

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METTL14 Promotes Ischemic Stroke-induced Brain Injury by Stabilizing HDAC3 Expression in an m6A-IGF2BP3 Mechanism

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Language: Английский

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