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

Linxia Lu,

Cili Jifu,

Jun Xia

et al.

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

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders DOI Creative Commons

Yejia Xu,

Bowen Jia,

Jing Li

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

Citations

24
Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation DOI Creative Commons
Dandan Liu,

Hewei Qin,

Yang Gao

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258

Published: June 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Language: Английский

Citations

23
Tailoring traditional Chinese medicine in cancer therapy DOI Creative Commons

Shuiquan Li,

Xi Chen, Hui Shi

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 21, 2025

Language: Английский

Citations

7
In defence of ferroptosis DOI Creative Commons
Francesca M. Alves, Darius J.R. Lane,

Triet Phu Minh Nguyen

et al.

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

6
Dinuclear Dicationic Iridium Complexes for Highly Synergistic Photodynamic and Photothermal Therapy to Chemoresistant Cancer DOI

Lizhen Zeng,

Xue‐Lian Li,

Yu‐Ang Deng

et al.

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT PTT) cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen superoxide anion, release heat when exposed to infrared (IR) irradiation, thus inducing reactive species (ROS)-associated cell disruption thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis. Additionally, the deplete intracellular glutathione, lead lipid peroxidation, induce ferroptosis. selected complex

Language: Английский

Citations

4
Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance DOI Creative Commons
Peng Zhao,

Shuangshuang Yin,

Yuling Qiu

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

Citations

4
IGF2BP1/AIFM2 axis regulates ferroptosis and glycolysis to drive hepatocellular carcinoma progression DOI
Wei Peng, Jie Liang,

Xuanlv Qian

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111660 - 111660

Published: Feb. 1, 2025

Language: Английский

Citations

3
Hippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1 DOI Creative Commons
Gang She,

Xia-Xia Hai,

Lin-Chun Jia

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103597 - 103597

Published: March 1, 2025

Language: Английский

Citations

3
Advanced Nanomaterials for Cancer Therapy: Gold, Silver, and Iron Oxide Nanoparticles in Oncological Applications DOI Creative Commons
Priyanka Singh, Santosh Pandit, Sri Renukadevi Balusamy

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(4)

Published: Nov. 6, 2024

Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed gold, silver, and iron oxide, have emerged as promising candidates changing cancer therapy. This comprehensive review demonstrates landscape nanoparticle-based oncological interventions, focusing on remarkable advancements potentials oxide nanoparticles. Gold nanoparticles garnered significant attention their exceptional biocompatibility, tunable surface chemistry, distinctive optical properties, rendering them ideal various diagnostic strategies. Silver nanoparticles, renowned antimicrobial exhibit potential in therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, drug delivery enhancement. With magnetic properties offer unique diagnosis targeted opportunities. critically examines recent synthesis, functionalization, biomedical applications these Moreover, challenges are discussed, toxicity concerns, immunogenicity, translational barriers, ongoing efforts to overcome hurdles highlighted. Finally, insights into future directions regulatory considerations, provided aiming accelerate translation technologies from bench bedside.

Language: Английский

Citations

15
METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma DOI Creative Commons
Jialin Wang,

Mengxi Xiu,

Jin Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 2, 2024

Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms m6A-related regulators HCC ferroptosis remain unclear. By examining series m6A enzymes upon induction or inhibition, we identified METTL16 novel ferroptotic repressor cells. The on development were investigated multiple lines, human organoids, subcutaneous xenografts MYC/Trp53−/− model hepatocyte-specific Mettl16 knockout overexpression mice. underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay Mass Spectrometry. clinical significance relevance evaluated samples. High expression confers resistance cells mouse models, promotes viability progression. Mechanistically, collaborates IGF2BP2 modulate SENP3 mRNA stability an m6A-dependent manner, latter impedes proteasome-mediated ubiquitination degradation Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF facilitates chelation free iron reduces liable pool level. are implicated METTL16-mediated progression anti-ferroptotic effects both vivo vitro. Clinically, positively correlated, high predicts poor prognosis Our study reveals new METTL16-SENP3-LTF signaling axis regulating driving development. Targeting this is strategy sensitizing against HCC.

Language: Английский

Citations

13