Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors DOI Creative Commons
Yuhang Huang, Zhen Chen, Jiang Chen

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 17, 2024

Abstract Degeneration of the cochlear spiral ganglion neurons (SGNs) is one major causes sensorineural hearing loss and significantly impacts outcomes implantation. Functional regeneration SGNs holds great promise for treating loss. In this study, we systematically screened 33 transcriptional regulators implicated in neuronal SGN fate. Using gene expression array principal component analyses, identified a sequential combination Ascl1, Pou4f1 Myt1l (APM) promoting functional reprogramming SGNs. The induced by APM expressed mature lineage‐specific markers, displayed SGN‐like electrophysiological characteristics exhibited single‐cell transcriptomes resembling endogenous Thus, transcription factors may serve as novel candidates direct recovery due to damages.

Language: Английский

FOXO1‐NCOA4 Axis Contributes to Cisplatin‐Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy DOI Creative Commons

Xue Wang,

Lei Xu, Yu Meng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(40)

Published: Aug. 29, 2024

Abstract Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage also render cochlear implants ineffective. However, the mechanisms underlying cisplatin‐induced SGNs subsequent SNHL still under debate there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis triggered in following exposure cisplatin. Inhibiting protects against loss, inducing intensifies these effects. Furthermore, prompts nuclear receptor coactivator 4 (NCOA4)‐mediated ferritinophagy SGNs, knocking down NCOA4 mitigates loss. Notably, upstream regulator of identified transcription factor forkhead box O1 (FOXO1) shown directly suppress expression SGNs. The FOXO1 amplifies NCOA4‐mediated ferritinophagy, increases lipid peroxidation, disrupting interaction between knock out mice prevents SGN Collectively, highlights critical role FOXO1‐NCOA4 axis regulating damage, offering promising therapeutic targets mitigation.

Language: Английский

Citations

12
Ferroptosis: iron release mechanisms in the bioenergetic process DOI
Jaewang Lee, Jong‐Lyel Roh

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 25, 2025

Language: Английский

Citations

1
SIRT3 regulates PFKFB3-mediated glycolysis to attenuate cisplatin-induced ototoxicity both in vivo and in vitro DOI
Wei Tang, Shimin Zong, Peiyu Du

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Language: Английский

Citations

0
Transforming Growth Factor‐β‐Activated Protein 1 (TAK1) Regulates Necroptosis in Age‐Related Hearing Loss DOI Creative Commons
Hanjing Wang,

Yayun Lv,

He Zhao

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

ABSTRACT Inflammation plays an important role in age‐related hearing loss (ARHL). Transforming growth factor‐β‐activated protein 1 (TAK1), a key factor upstream of inflammatory pathways, mediates various cell death potentially influencing the survival and cochlear hair cells. The DBA/2 J mouse model HEI‐OC1 line were used to investigate mechanism TAK1‐mediated inflammation ARHL. Hematoxylin eosin staining revealed significant histological damage cochlea 16‐week‐old mice, along with increase auditory‐evoked brainstem response thresholds. Concurrently, TAK1 mRNA levels decreased sharply, necroptosis significantly increased indicating correlation between expression, necroptosis, loss. We subsequently constructed knockdown overexpression cells for further investigation. activated necroptotic pathway, characterized by up‐regulation RIPK3 MLKL , down‐regulation NF‐κB Caspase 8 . However, successfully prevented cells, leading decreases treated inhibitors found that they could reverse caused This preliminary study shows pathways play pathogenesis

Language: Английский

Citations

0
Pinoresinol Diglucoside Attenuates Nuclear Receptor Coactivator 4‐Mediated Ferritinophagy Associated with Cisplatin‐Induced Hearing Loss DOI Creative Commons
Yin Chen, Cheng Cheng, Ao Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Cisplatin can cause irreversible hearing loss. However, effective approaches to its prevention are not established. In this study, the effect of traditional Chinese medicine monomer pinoresinol diglucoside (PDG) is evaluated on cisplatin-induced ototoxicity and underlying mechanism action. PDG significantly increases cell viability inhibits reactive oxygen species production ferroptosis in cisplatin-treated House Ear Institute-Organ Corti 1 cells basilar membranes. partially restores loss caused by cisplatin. Transcriptome sequencing identifies Suppressor Cytokine Signaling (SOCS1), which elevated cisplatin-only group but reduced after application. SOCS1 a ferroptosis-promoting factor, knocking it down nuclear receptor coactivator 4 (NCOA4) ferritinophagy. Transmission electron microscopy reveals that reduces number autophagic lysosomes induced Co-immunoprecipitation performed confirm interaction between NCOA4. Taken together, these results indicate NCOA4-mediated ferritinophagy downregulating SOCS1, ototoxicity. This study provides new clinical option for

Language: Английский

Citations

0
Ferroptosis regulation by traditional chinese medicine for ischemic stroke intervention based on network pharmacology and data mining DOI Creative Commons
Jun Lei, Wei Chen, Yaodong Gu

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0321751 - e0321751

Published: April 16, 2025

Objective The aim of this study is to use network pharmacology and data mining explore the role traditional Chinese medicine (TCM) in ischemic stroke (IS) intervention by ferroptosis regulation. results will provide reference for related research on IS. Methods ferroptosis-related targets were obtained from GeneCards, GeneCLiP3, FerrDdb databases, while IS sourced GeneCards DisGeNET databases. Venny was used identify associated with ferroptosis. A protein-protein interaction (PPI) analysis then conducted, machine learning screening validate these potential targets. that met specific criteria their compounds allowed us select TCMs. mechanistic conducted using DAVID database. PPI diagrams, target-compound target-compound-TCM diagrams constructed. Finally, molecular docking technology verify binding activities TCM core components identified In addition, properties, flavors, meridian tropism, therapeutic effects candidate TCMs analyzed statistically evaluated. Results total 706 obtained, 14 learning. Furthermore, 413 301 screened, prescriptions stable. primarily exhibited cold, warm, bitter taste, pungent liver meridian, heat-cleaning medicinal, tonify deficiency properties. Conclusions This investigated regulation TCM. We began investigating ferroptosis, we also relevant mechanism

Language: Английский

Citations

0
Targeting Programmed Cell Death in Acquired Sensorineural Hearing Loss: Ferroptosis, Necroptosis, and Pyroptosis DOI Creative Commons
Shasha Zhang,

Hairong Xiao,

Yanqin Lin

et al.

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

Citations

0
VDAC1 Inhibition Protects Against Noise‐Induced Hearing Loss via the PINK1/Parkin Pathway DOI Creative Commons

Yuchen Jin,

Wenqi Dong,

Yumeng Jiang

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(4)

Published: April 1, 2025

ABSTRACT Aims This study examined the effect of 4,4′‐diisothiocyanostilbene‐2,2′‐disulfonic acid (DIDS), an anion channel blocker voltage‐dependent 1 (VDAC1), on noise‐induced hearing loss (NIHL) and its underlying mechanisms. Methods Cochlear explants House Ear Institute‐Organ Corti (HEI‐OC1) cells were used to assess DIDS in vitro. Auditory brainstem responses auditory functions mice. Immunofluorescence staining myosin 7a CTBP2 examine hair synaptic ribbons. The accumulation reactive oxygen species (ROS) was measured by 4‐HNE staining. gene expression changes cochlea analyzed using RNA sequencing. Results reduced levels ROS cochlear attenuated cell death caused hydrogen peroxide both HEI‐OC1 cells. In C57BL/6 mice, generation tumor necrosis factor‐α induced noise exposure, thereby protecting outer inner ribbons from damage through a mechanism involving PINK1/Parkin signaling pathway. preventive eliminated mitophagy inhibition. Conclusion VDAC1 inhibition enhances cells, playing critical role defending against oxidative stress inflammation. Downregulation may thus be considered therapeutic strategy for preventing reducing NIHL.

Language: Английский

Citations

0
Selenomethionine suppresses lung tumor growth without hepatorenal toxicity in mice via the induction of apoptosis-ferroptosis and angiogenesis inhibition DOI

Houru Liu,

Caiyun Zhang, Lejun Zhang

et al.

Tissue and Cell, Journal Year: 2025, Volume and Issue: 96, P. 102956 - 102956

Published: May 10, 2025

Language: Английский

Citations

0
The key role of the ferroptosis mechanism in neurological diseases and prospects for targeted therapy DOI Creative Commons
Chengyu Xie, Nan Wu, Jiaojiao Guo

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: May 12, 2025

Neurological disorders represent a major global health concern owing to their intricate pathological processes. Ferroptosis, defined as form of cell death that is reliant on iron, has been closely linked various neurological conditions. The fundamental process underlying ferroptosis by the excessive buildup iron ions, which initiates lipid peroxidation processes leading cellular demise. Neurons, highly metabolically active cells, are susceptible oxidative stress, and imbalances in metabolism can directly initiate process. In neurodegenerative like Alzheimer's disease Parkinson's disease, driven accumulation represents connection. Although connection between diseases clear, clinical application still faces challenges, such precise regulation metabolism, development specific drugs, assessment efficacy. limited comprehension mechanism hinders personalized treatment approaches. Consequently, subsequent investigations must tackle these obstacles facilitate ferroptosis-associated therapies disorders. This article provides comprehensive overview most recent advancements regarding mechanisms ferroptosis. Subsequently, study investigates mechanistic contributions within nervous system. conclusion, we evaluate deliberate targeted therapeutic strategies associated with

Language: Английский

Citations

0