Iron homeostasis imbalance and ferroptosis in brain diseases DOI Creative Commons
Haining Long,

Wangshu Zhu,

Liming Wei

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: June 26, 2023

Brain iron homeostasis is maintained through the normal function of blood-brain barrier and regulation at systemic cellular levels, which fundamental to brain function. Excess can catalyze generation free radicals Fenton reactions due its dual redox state, thus causing oxidative stress. Numerous evidence has indicated diseases, especially stroke neurodegenerative are closely related mechanism imbalance in brain. For one thing, diseases promote accumulation. another, accumulation amplifies damage nervous system exacerbates patients' outcomes. In addition, triggers ferroptosis, a newly discovered iron-dependent type programmed cell death, neurodegeneration received wide attention recent years. this context, we outline metabolism focus on current stroke, Alzheimer's disease, Parkinson's disease. Meanwhile, also discuss ferroptosis simultaneously enumerate drugs for chelators inhibitors.

Language: Английский

Contribution of ferroptosis and GPX4’s dual functions to osteoarthritis progression DOI
Miao Yu, Yiwei Chen, Feng Xue

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 76, P. 103847 - 103847

Published: Feb. 1, 2022

Language: Английский

Citations

306
Oxidative stress and regulated cell death in Parkinson’s disease DOI
Pedro A. Dionísio, Joana D. Amaral, Cecília M. P. Rodrigues

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 67, P. 101263 - 101263

Published: Feb. 2, 2021

Language: Английский

Citations

296
Phospholipase iPLA2β averts ferroptosis by eliminating a redox lipid death signal DOI
Wan‐Yang Sun, Vladimir A. Tyurin, Karolina Mikulska‐Ruminska

et al.

Nature Chemical Biology, Journal Year: 2021, Volume and Issue: 17(4), P. 465 - 476

Published: Feb. 4, 2021

Language: Английский

Citations

245
New Insights into the Role of Ferritin in Iron Homeostasis and Neurodegenerative Diseases DOI
Na Zhang,

Xiao‐Qi Yu,

Junxia Xie

et al.

Molecular Neurobiology, Journal Year: 2021, Volume and Issue: 58(6), P. 2812 - 2823

Published: Jan. 28, 2021

Language: Английский

Citations

147
Trial of Deferiprone in Parkinson’s Disease DOI Open Access
David Devos, Julien Labreuche, Olivier Rascol

et al.

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 387(22), P. 2045 - 2055

Published: Nov. 30, 2022

Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to pathophysiology disorder. Early research suggests that iron chelator deferiprone can reduce nigrostriatal disease, but its effects on progression are unclear.

Language: Английский

Citations

139
The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities DOI Creative Commons

Kamari Weaver,

Rachid Skouta

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

133
Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutant colorectal cancer DOI Creative Commons
Hao Chen, Qinqin Qi, Nan Wu

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 55, P. 102426 - 102426

Published: Aug. 4, 2022

Ferroptosis, a new form of regulated cell death triggered by the iron-dependent peroxidation phospholipids, is associated with cellular metabolism, redox homeostasis, and various signaling pathways related to cancer. Aspirin widely used non-steroidal anti-inflammatory drug (NSAID) has been reported show therapeutic benefit in cancers harboring oncogenic PIK3CA, which encodes catalytic p110α subunit phosphoinositide 3-kinase (PI3K). In this study, we found that aspirin sensitized cancer cells activation PIK3CA ferroptosis induction. Mechanistically, inhibited protein kinase B (AKT)/mammalian target rapamycin (mTOR) signaling, suppressed downstream sterol regulatory element-binding 1 (SREBP-1) expression, attenuated stearoyl-CoA desaturase-1 (SCD1)-mediated lipogenesis monounsaturated fatty acids, thus promoting RSL3-induced colorectal (CRC) cells. Moreover, genetic ablation SREBP-1 or SCD1 conferred greater sensitivity Conversely, ectopic expression restored resistance CRC abolished effect on cytotoxicity. Additionally, synergistic effects RSL3 were confirmed xenograft mouse model. The combined use resulted significant tumor suppression. Our work demonstrated enhanced cytotoxic PIK3CA-mutant cancers, combination inducer displayed promising treatment.

Language: Английский

Citations

105
Quercetin Protects against MPP+/MPTP-Induced Dopaminergic Neuron Death in Parkinson’s Disease by Inhibiting Ferroptosis DOI Creative Commons
Zhihao Lin, Yi Liu,

Nai‐Jia Xue

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 17

Published: Sept. 5, 2022

Ferroptosis, a novel form of regulated cell death, is caused by accumulation lipid peroxides and excessive iron deposition. This process has been linked to the death dopaminergic neurons in substantia nigra compacta (SNc) Parkinson's disease (PD) patients. Quercetin (QCT), natural flavonoid, multiple pharmacological activities. However, it not established whether QCT can protect against neuron inhibiting ferroptosis. In this study, we investigated potential antiferroptotic effects cellular models using specific ferroptosis inducers (Erastin RSL-3) MPP+. The were also explored MPTP-induced PD mouse models. counting kit-8 (CCK-8) assay was performed assess viability. Variations mitochondrial morphology evaluated transmission electron microscopy (TEM) while membrane potential, mass, ROS measured fluorescent probes. Lipid peroxidation levels assayed through measurement ROS, MDA, GSH, SOD levels. on behavioral disorders examined rotarod open field tests. vitro vivo, significantly inhibited activating nuclear factor erythroid 2-related 2 (Nrf2) protein. Additionally, ameliorated motor impairments protected loss Interestingly, Nrf2 knockdown alleviated protective conclusion, these results demonstrate that involved MPP+/MPTP-induced PD, inhibits Therefore, agent for preventing targeting

Language: Английский

Citations

104
Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity DOI Creative Commons
Jinjin Jiang, Guofu Zhang,

Jia-Yi Zheng

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: April 12, 2022

Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, was reported to be capable inhibiting ferroptosis, which is a recognized type regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression NAFLD, experimental evidence limited. Hence, our study aimed investigate high-fat diet (HFD)-induced NAFLD and further elucidate underlying molecular mechanism. Methods: C57BL/6J mice were fed either normal (ND), HFD, or HFD supplemented with for 12 weeks. Hepatic lipid peroxidation, steatosis, iron overload examined. In vitro, steatotic L-02 cells used potential Results: We found that caused accumulation liver, rescued by supplementation. Consistent vivo results, alleviated droplet reduced levels reactive oxygen species (ROS) cells. Using mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) specific inhibitor (Fer-1), we remarkably peroxidation reducing MtROS-mediated Conclusion: Our data showed consumption induced triggered ultimately leading lipotoxicity, can quercetin. Findings from this provide new insight into prevention treatment NAFLD.

Language: Английский

Citations

92
Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes DOI Creative Commons
Yumin Wang, Shuang Wu, Qiang Li

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(24)

Published: June 21, 2023

Emerging evidence suggests that ferroptosis, a unique regulated cell death modality is morphologically and mechanistically different from other forms of death, plays vital role in the pathophysiological process neurodegenerative diseases, strokes. Accumulating supports ferroptosis as critical factor diseases strokes, pharmacological inhibition therapeutic target for these diseases. In this review article, core mechanisms are overviewed roles strokes described. Finally, emerging findings treating through This demonstrates by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective treatments highlights potential promising avenue used to prevent article will shed light on developing novel regimens slow down progression future.

Language: Английский

Citations

88