Ferroptosis and Charcot–Marie–Tooth Disease 1A: Emerging Evidence for a Pathogenic Association DOI Creative Commons

Jacob B. White,

Kayla L. Sanchez, António Currais

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 331 - 331

Published: March 11, 2025

Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy worldwide, presenting clinically as muscle weakness that progresses to impaired ambulation or quadriplegia with age. CMT1A, subtype, caused by a duplication in PMP22, encoding an essential membrane protein for Schwann cell myelin integrity. While mechanisms of neurodegeneration CMT1A are poorly understood, excessive oxidative stress, particularly lipid peroxidation, known pathological feature, and antioxidant therapy has reversed phenotype mouse model. For first time, we define pathogenic link between ferroptosis, form regulated death peroxidation hindered defenses. Human-derived fibroblasts showed greater susceptibility RSL3, pro-ferroptosis agent, compared controls, alongside several ferroptosis markers, including elevated peroxides depleted GPX4, critical anti-ferroptosis repressor. Similarly, transcriptomic analysis human iPSC-derived cells revealed activation cellular stress markers CMT1A. We propose chronic, sublethal ferroptotic mediated peroxide accumulation, depletes defenses cells, leading decompensation age, manifesting symptomatic disease. These results emphasize driver pathology, potentially revealing new therapeutic path.

Language: Английский

A guide to cell death pathways DOI
Junying Yuan, Dimitry Ofengeim

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 379 - 395

Published: Dec. 18, 2023

Language: Английский

Citations

272
Ironing out the role of ferroptosis in immunity DOI Creative Commons
Hannah N. Bell, Brent R. Stockwell, Weiping Zou

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(5), P. 941 - 956

Published: May 1, 2024

Ferroptosis is a type of regulated cell death that drives the pathophysiology many diseases. Oxidative stress detectable in types death, but only ferroptosis involves lipid peroxidation and iron dependency. originates propagates from several organelles, including mitochondria, endoplasmic reticulum, Golgi, lysosomes. Recent data have revealed immune cells can both induce undergo ferroptosis. A mechanistic understanding how regulates immunity critical to controls responses this dysregulated disease. Translationally, more work needed produce ferroptosis-modulating immunotherapeutics. This review focuses on role immune-related diseases, infection, autoimmune cancer. We discuss immunity, regulation contributes disease pathogenesis, targeting may lead novel therapies.

Language: Английский

Citations

48
Ginsenoside Rg1 alleviates chronic inflammation-induced neuronal ferroptosis and cognitive impairments via regulation of AIM2 - Nrf2 signaling pathway DOI
Liangliang Kong, Yan Liu, Jingwei Li

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 330, P. 118205 - 118205

Published: April 17, 2024

Language: Английский

Citations

14
Ferroptosis in Parkinson's disease —— The iron-related degenerative disease DOI

Zhengyang Yao,

Qian Jiao, Xixun Du

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102477 - 102477

Published: Aug. 31, 2024

Language: Английский

Citations

10
Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets DOI
Fernanda V. Carvalho,

Harold E. Landis,

Bruk Getachew

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 105 - 132

Published: Jan. 1, 2024

Language: Английский

Citations

9
Polycatechols inhibit ferroptosis and modulate tau liquid–liquid phase separation to mitigate Alzheimer's disease DOI
Hariharan Moorthy, Madhu Ramesh,

Dikshaa Padhi

et al.

Materials Horizons, Journal Year: 2024, Volume and Issue: 11(13), P. 3082 - 3089

Published: Jan. 1, 2024

Polycatechols modulate amyloid-associated toxicities, arrest labile iron, inhibit lipid peroxidation, and regulate tau liquid–liquid phase separation (LLPS) to mitigate the pathological nexus between ferroptosis AD.

Language: Английский

Citations

9
Mifepristone protects acetaminophen induced liver injury through NRF2/GSH/GST mediated ferroptosis suppression DOI
Yanyun Shi,

Nahua Xu,

B Liu

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 222, P. 229 - 243

Published: June 19, 2024

Language: Английский

Citations

9
Ferroptosis: mechanisms and therapeutic targets DOI Creative Commons
Qian Zhou, Yu Meng,

Jiayuan Le

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

Language: Английский

Citations

9
O-GlcNAcylation attenuates ischemia-reperfusion-induced pulmonary epithelial cell ferroptosis via the Nrf2/G6PDH pathway DOI Creative Commons
Liuqing Yang, Hexiao Tang, Jin Wang

et al.

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Lung ischemia–reperfusion (I/R) injury is a common clinical pathology associated with high mortality. The pathophysiology of lung I/R involves ferroptosis and elevated protein O-GlcNAcylation levels, while the effect on remains unclear. This research aimed to explore reducing in pulmonary epithelial cells caused by I/R. First, we identified O-GlcNAc transferase 1 (Ogt1) as differentially expressed gene acute injury/acute respiratory distress syndrome (ALI/ARDS) patients, using single-cell sequencing, Gene Ontology analysis (GO analysis) revealed enrichment process. We found time-dependent dynamic alteration during injury. Proteomics proteins enriched multiple redox-related pathways based KEGG annotation. Thus, generated Ogt1-conditional knockout mice that Ogt1 deficiency aggravated ferroptosis, evidenced lipid reactive oxygen species (lipid ROS), malondialdehyde (MDA), Fe2+, well alterations critical expression glutathione peroxidase 4 (GPX4) solute carrier family 7 member 11 (SLC7A11). Consistently, inhibited sensitivity hypoxia/reoxygenation (H/R) injury-induced TC-1 via O-GlcNAcylated NF-E2-related factor-2 (Nrf2). Furthermore, both chromatin immunoprecipitation (ChIP) assay dual-luciferase reporter indicated Nrf2 could bind translation start site (TSS) glucose-6-phosphate dehydrogenase (G6PDH) promote its transcriptional activity. As an important rate-limiting enzyme pentose phosphate pathway (PPP), G6PDH provided mass nicotinamide adenine dinucleotide (NADPH) improve redox state (GSH) eventually led resistance. Rescue experiments proved knockdown or Nrf2-T334A (O-GlcNAcylation site) mutation abolished protective In summary, protect against Nrf2/G6PDH pathway. Our work will provide new basis for therapeutic strategies ischemia–reperfusion-induced

Language: Английский

Citations

1
Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis DOI Creative Commons
Alejandro Marmolejo-Garza, Inge E. Krabbendam,

Minh Danh Anh Luu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(11)

Published: Nov. 25, 2023

Abstract Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of regulated cell death, that has been implicated in Alzheimer’s disease Parkinson’s disease. Inhibition cystine/glutamate antiporter could lead to mitochondrial fragmentation, calcium ([Ca 2+ ] m ) overload, increased ROS production, disruption the membrane potential (ΔΨ ), ferroptotic death. The observation dysfunction a characteristic ferroptosis makes preservation function therapeutic option for diseases associated with Mitochondrial levels are controlled via uniporter (MCU), main entry point Ca into matrix. Therefore, we have hypothesized negative modulation MCU complex may confer protection against ferroptosis. Here evaluated whether known modulators complex, ruthenium red (RR), its derivative Ru265, mitoxantrone (MX), MCU-i4 can prevent These compounds mediated HT22 cells, human dopaminergic neurons mouse primary cortical Depletion MICU1, [Ca gatekeeper, demonstrated MICU protective Taken together, our results reveal represents degenerative conditions, which central progression these pathologies.

Language: Английский

Citations

21