Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: June 6, 2024
Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.
Language: Английский
Citations
52
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 273, P. 116520 - 116520
Published: May 21, 2024
Language: Английский
Citations
14
Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103259 - 103259
Published: June 27, 2024
Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, modification. modifications play pivotal roles in regulating protein stability, activity, localization, interactions, ultimately influencing both the buildup iron lipid peroxidation. In mammalian cells, regulators ferroptosis typically degradation via two principal pathways: ubiquitin-proteasome which handles majority degradation, autophagy, primarily targeting long-lived or aggregated This comprehensive review aims to summarize recent advances modification linked ferroptosis. It also discusses strategies for modulating systems, providing new insights into potential therapeutic applications cancer non-neoplastic diseases.
Language: Английский
Citations
14
Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 2485 - 2529
Published: June 1, 2024
Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess iron accumulation and lipid peroxidation-induced damage. There growing body evidence indicating that ferroptosis plays critical role in the advancement tumors. The increased metabolic activity higher levels tumor cells make them particularly vulnerable to ferroptosis. As result, targeted induction becoming increasingly promising approach for cancer treatment. This review offers overview regulatory mechanisms ferroptosis, delves into mechanism action traditional small molecule inducers their effects on various In addition, latest progress inducing using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic (SDT) nanomaterials summarized. Finally, this discusses challenges opportunities development ferroptosis-inducing agents, focusing discovering targets, improving selectivity, reducing toxic side effects. Keywords: inducers, molecules, PROTACs, PDT, SDT,
Language: Английский
Citations
9
Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 29, 2025
Linker structures are a crucial component of proteolysis-targeting chimeras (PROTACs) and have traditionally been designed based on empirical methods, which presents significant challenges in the development PROTACs. Current optimization strategies typically focus reducing number rotatable bonds linker to limit conformational freedom. However, this approach overlooks complexity target protein degradation process. Retrospective analyses suggest that merely adjusting is insufficient control freedom PROTACs, indicating need for new strategies. By integration computational methods such as molecular dynamics simulations, study investigates role throughout induction process, particularly its impact formation stability ternary complex. This offers potential overcoming limitations traditional strategies, reliance enhancing overall efficiency effectiveness PROTAC design.
Language: Английский
Citations
1
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 274, P. 116548 - 116548
Published: May 31, 2024
Language: Английский
Citations
7
Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10
Published: Sept. 25, 2023
Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with 5-year survival rate of less than 30%. Continuous updating diagnostic and therapeutic strategies has not been effective in improving the clinical benefit AML. AML cells are prone to iron metabolism imbalance due their unique pathological characteristics, ferroptosis novel cell death mode that dominated by three cellular biological processes: metabolism, oxidative stress lipid metabolism. An in-depth exploration mechanism can provide new insights for diagnosis treatment this disease. This study summarizes recent studies on suggests metabolic gene mutation patterns, dependence mitochondria greatly increase susceptibility ferroptosis. In addition, establish variety evade maintain during process occurrence development, related drugs targeting pathway treatment, which provides development directions subsequent research
Language: Английский
Citations
13
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: Feb. 12, 2024
Abstract Background Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties RSL3 limited its clinical application. Here, we investigated synergism non-thermal plasma (NTP) low-concentration attempted to rise sensitivity NSCLC RSL3. Methods CCK-8 assay was employed detect change cell viability. Microscopy flowcytometry were applied identify lipid peroxidation, death reactive oxygen species (ROS) level respectively. The mechanism inspected with western blot RT-qPCR. A xenograft mice model adopted investigate effect NTP Results We found triggered severe mitochondria damage, more rapid ferroptosis occurrence vitro vivo. synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, revealed mitochondrial ROS main executor for by combined treatment. Conclusion Our shows treatment promoted toxic inducing rapidly provided possibility Graphical
Language: Английский
Citations
6
Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 221, P. 23 - 30
Published: May 11, 2024
Language: Английский
Citations
6
Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e24857 - e24857
Published: Jan. 26, 2024
At present, GPX4's role in the occurrence and development of diffuse large B lymphoma (DLBCL) is rarely reported. This study's purpose to explore significance diagnosis, treatment, pathological mechanisms DLBCL. The TIMER 2.0, GEPIA, GEO databases were used analyze expression levels DLBCL tissue, peripheral blood, single cells, evaluate its potential performance as a therapeutic diagnostic marker. Cell experiments validate cells. And revealed mechanism action from three aspects: immunity, pathogenic gene expression, protein interaction. results indicate that GPX4 can be biomarker for treatment diagnosis (FC > 1.5, P < 0.05, AUC>0.8, KM-P value 0.05). In cell data, also showed high immune Besides, have confirmed inhibit cells' proliferation. Meanwhile, we found negative correlation between 16 core DLBCL's genes, significant with infiltration. summary, serve marker lead good prognosis patients, which may related inhibition cancer proliferation, key infiltration
Language: Английский
Citations
5