Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2023, Volume and Issue: 1870(6), P. 119480 - 119480
Published: April 30, 2023
Language: Английский
Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 891 - 891
Published: April 13, 2022
The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in human body. Its central function involves reduction complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become hotspot therapeutic target biomedical research following its characterization chief regulator ferroptosis, and subsequent recognition specific pharmacological for treatment an extensive variety diseases including cancers neurodegenerative disorders. Several recent studies have provided insights how distinguished from rest family, unique biochemical properties GPX4, related to lipid peroxidation enzyme may be modulated potential target. This current report aims review literature underlying all these present up-to-date perspective on understanding
Language: Английский
Citations
130
Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2726 - 2726
Published: Sept. 1, 2022
Ferroptosis has recently been demonstrated to be a novel regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation that results in membrane damage. Excessive iron induces ferroptosis promoting generation both soluble ROS via an iron-dependent Fenton reaction lipoxygenase (LOX) enzyme activity. Cytosolic glutathione peroxidase 4 (cGPX4) pairing with suppressor protein 1 (FSP1) mitochondrial (mGPX4) dihydroorotate dehydrogenase (DHODH) serve as two separate defense systems detoxify cytoplasmic well membrane, thereby defending against cells under normal conditions. However, disruption these may cause ferroptosis. Emerging evidence revealed plays essential role development diverse cardiovascular diseases (CVDs), such hemochromatosis-associated cardiomyopathy, doxorubicin-induced cardiotoxicity, ischemia/reperfusion (I/R) injury, heart failure (HF), atherosclerosis, COVID-19–related arrhythmias. Iron chelators, antioxidants, inhibitors, genetic manipulations alleviate aforementioned CVDs blocking pathways. In conclusion, critical pathogenesis various suppression cardiac is expected become potential therapeutic option. Here, we provide comprehensive review on molecular mechanisms involved its implications disease.
Language: Английский
Citations
101
Biomolecules, Journal Year: 2022, Volume and Issue: 12(5), P. 714 - 714
Published: May 17, 2022
Disruption of cerebral iron regulation appears to have a role in aging and the pathogenesis various neurodegenerative disorders. Possible unfavorable impacts accumulation include reactive oxygen species generation, induction ferroptosis, acceleration inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow examination macroscopic patterns brain deposits vivo, while modern analytical methods ex vivo enable determination metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes whole brain, cellular, subcellular diseases genetic sporadic origin. We provide an update on mechanisms, biomarkers, effects these disorders, focusing recent publications. In Parkinson’s disease, Friedreich’s several disorders neurodegeneration with group, there is focal siderosis, typically regions most pronounced neuropathological second group including multiple sclerosis, Alzheimer’s amyotrophic lateral sclerosis shows globus pallidus, caudate, putamen, cortical regions. Yet, other such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest diffuse deep gray matter pattern comparable even more extensive than that observed during normal aging. On microscopic level, are mostly dystrophic microglia variably accompanied by iron-laden macrophages astrocytes, implicating changes blood–brain barrier disturbance accumulation. Options potential benefits reducing strategies discussed. Future research investigating whether predispositions play Fe necessary. If confirmed, prevention further uptake individuals at risk may be key for preventing
Language: Английский
Citations
90
Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(18), P. 7752 - 7778
Published: Jan. 1, 2022
Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death driven by excessive lipid peroxidation (LPO). Mounting evidence suggests that the unique modality involved in development and progression several diseases including cancer, cardiovascular (CVDs), neurodegenerative disorders, etc. However, pathogenesis signalling pathways ferroptosis are not fully understood, possibly due to lack robust tools for highly selective sensitive imaging analytes complex living systems. Up now, various small-molecule fluorescent probes have been applied as promising chemosensors studying through tracking biomolecules or microenvironment-related parameters vitro vivo. In this review, we comprehensively reviewed recent ferroptosis, with a focus on analytes, design strategies bioimaging applications. We also provided new insights overcome major challenges emerging field.
Language: Английский
Citations
88
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512
Published: April 3, 2024
GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.
Language: Английский
Citations
58
Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)
Published: April 22, 2024
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) has garnered considerable attention globally. Changing lifestyles, over-nutrition, and physical inactivity have promoted its development. MASLD is typically accompanied by obesity strongly linked to metabolic syndromes. Given that prevalence on the rise, there an urgent need elucidate pathogenesis. Hepatic lipid accumulation generally triggers lipotoxicity induces or progress steatohepatitis (MASH) mediating endoplasmic reticulum stress, oxidative organelle dysfunction, ferroptosis. Recently, significant been directed towards exploring role of gut microbial dysbiosis in development MASLD, offering a novel therapeutic target for MASLD. Considering are no recognized pharmacological therapies due diversity mechanisms involved difficulty associated with undertaking clinical trials, potential targets remain elusive. Thus, this article aimed summarize evaluate prominent roles lipotoxicity, ferroptosis, microbes underlying their effects. Furthermore, existing advances challenges treatment were outlined.
Language: Английский
Citations
45
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: April 30, 2024
With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal tissue structure reduced strength in patients with diabetes. Studies have revealed close association among diabetes, increased fracture risk, disturbances iron metabolism. This review explores concept of ferroptosis, non-apoptotic cell death process dependent on intracellular iron, focusing its role DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) osteoclasts (OCs), contributes to The intricate interplay between dysregulation, which comprises deficiency overload, DOP has been discussed, emphasizing how excessive accumulation triggers ferroptosis concise overview highlights need understand complex relationship T2DM OP, ferroptosis. aimed elucidate pathogenesis provide prospective for future research targeting interventions field
Language: Английский
Citations
17
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Feb. 18, 2025
Language: Английский
Citations
8
Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 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.
Language: Английский
Citations
4
Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 153, P. 113279 - 113279
Published: June 20, 2022
Heart disease is the leading cause of death worldwide. Cardiomyopathy a characterized by heart muscle damage, resulting in structurally and functionally change, as well failure sudden cardiac death. The key pathogenic factor cardiomyopathy loss cardiomyocytes, but related molecular mechanisms remain unclear. Ferroptosis newly discovered regulated form cell death, iron accumulation lipid peroxidation during Recent studies have shown that ferroptosis plays an important regulatory roles occurrence development many diseases such myocardial ischemia/reperfusion injury, failure. However, systemic association remains largely unknown needs to be elucidated. In this review, we provide overview its role individual cardiomyopathies, highlight targeting maybe potential therapeutic strategy for therapy future.
Language: Английский
Citations
62