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

4-Hydroxyestrogen Metabolites Strongly Prevent Chemically-Induced Ferroptotic Hepatocyte Injury In Vitro and In Vivo DOI Creative Commons
Qi Zhang,

Xiangyu Hao,

Xi Sun

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177313 - 177313

Published: Feb. 1, 2025

Language: Английский

Citations

0
SIRT6 inhibits endoplasmic reticulum stress-mediated ferroptosis by activating Nrf2/HO-1 signaling to alleviate osteoarthritis DOI
Jiaqi Shi, Li Chen, Xu Wang

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Feb. 10, 2025

Language: Английский

Citations

0
KEAP1‐NRF2/HO‐1 Pathway Promotes Ferroptosis and Neuronal Injury in Schizophrenia DOI Creative Commons
Feng Zhu, Dan Tang,

Sherwin E. Hua

et al.

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 28, 2025

ABSTRACT Background This study investigates the role of KEAP1‐NRF2/HO‐1 signaling pathway in inducing ferroptosis and contributing to neuronal damage schizophrenia. Methods We retrieved schizophrenia‐related data ferroptosis‐related genes from RNA microarray dataset GSE27383 FerrDB database, respectively. Bioinformatics identified KEAP1 as a downregulated gene, which was validated using qRT‐PCR Western blot. assessed intracellular Fe 2 ⁺ content, MDA levels, GSH, GPX4 prefrontal cortex peripheral blood mononuclear cells (PBMCs) patients with Cortical interneurons (cINs) were generated human‐induced pluripotent stem (hiPSCs) schizophrenia used explore alterations during neurodevelopment. In addition, overexpression induced cINs via transfection pcDNA KEAP1. The Fe⁺ oxidative stress indicators, lipid peroxidation, inflammatory cytokines measured after transfection. To investigate molecular mechanisms, KI696—a high‐affinity probe that disrupts KEAP1–NRF2 interaction—was applied, changes stress, peroxidation (C11‐BODIPY staining), iron metabolism, pathways evaluated. Results Patients exhibited underexpression KEAP1, key regulator ferroptosis, along elevated levels increased concentrations, indicating enhanced stress. Reduced activity GSH also observed, suggesting an susceptibility ferroptosis. further this, derived hiPSCs studied. These showed decreased expression. Overexpression led reduction concentrations damage, highlighting KEAP1's regulatory treatment KI696 significant related antioxidant defenses, inflammation. Conclusion Our findings indicate contributes injury

Language: Английский

Citations

0
Aflatoxin B1 exposure induces Alzheimer's disease like pathology by disrupting redox homeostasis and activating ferroptotic signals in C57BL/6 J mice DOI
Jinxian Lin, Huihui Hong,

Sicheng Liu

et al.

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 970, P. 179049 - 179049

Published: March 1, 2025

Language: Английский

Citations

0
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

Citations

0