Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 10, 2025

Ferroptosis pathway activation is potentially correlated with temporal lobe epilepsy (TLE). However, the diagnostic significance and mechanism of ferroptosis-related genes (FRGs) in TLE require further investigation. A comprehensive analysis GSE134697 dataset from Gene Expression Omnibus (GEO) database using Weighted gene co-expression network (WGCNA) identified 3,212 differentially expressed (DEGs) between (TLE) control groups, a critical focus on turquoise module. Through intersection DEGs key module genes, correlation analyses functional-related (FRG), protein-protein interactions (PPI), least absolute shrinkage selection operator (LASSO), machine learning methods, five potential biomarkers ferroptosis (CBS, SHMT1, RIN3, QDPR, PLPP4) were isolated. nomogram was constructed these markers, enrichment revealed their links to T-cell activation, allograft rejection, glial differentiation. Variations 13 immune cell types also noted. Upregulation CBS, PLPP4 confirmed through RT-qPCR Western blot assays. Additionally, SHMT1-targeting one CBS-targeting drugs predicted Drug-Gene Interaction Database (DGIdb). These findings provide new insights into pathogenesis suggest targets for future research.

Language: Английский

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GrpEL1 overexpression mitigates hippocampal neuron damage via mitochondrial unfolded protein response after experimental status epilepticus

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: 206, P. 106838 - 106838

Published: Feb. 10, 2025

Despite the availability of various antiepileptic treatments, approximately 30 % epilepsy patients remain refractory to conventional therapies, underscoring need for neuroprotective strategies. This study investigates role GrpEL1 in modulating mitochondrial unfolded protein response (UPRmt) and its potential protective effects on hippocampal neurons following experimental status epilepticus (SE). The were assessed vivo using a Lithium-pilocarpine rat model SE vitro with glutamate-treated HT22 cells. Protein expression interactions analyzed by Western blot, immunofluorescence, co-immunoprecipitation. Neuronal survival was evaluated through Nissl staining. Mitochondrial function aggresome formation, membrane (MMP) assays, oxygen consumption rate (OCR) measurements, behavioral assessments Morris water maze. In model, mtHSP70 levels significantly upregulated mitochondria, while remained relatively stable. Overexpression led reduction neuronal damage improved functional recovery post-SE. vitro, overexpression enhanced GrpEL1-mtHSP70 interaction, reduced accumulation misfolded proteins, decreased apoptosis. Furthermore, mitigated dysfunction preserving MMP improving bioenergetics, as evidenced OCR. plays crucial maintaining proteostasis mitigating injury regulating UPRmt. These findings suggest that may represent promising target therapeutic intervention protect against seizure-induced neurodegeneration.

Language: Английский

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Mechanistic role of environmental toxicants in inducing cellular ferroptosis and its associated diseases

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 298, P. 118269 - 118269

Published: May 10, 2025

Language: Английский

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Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(8)

Published: Aug. 20, 2024

Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum conditions, including Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), Huntington’s (HD), epilepsy, brian ischemia, injury, neurodegeneration with brain iron accumulation (NBIA). Despite considerable heterogeneity in their clinical presentation, pathophysiological underpinning trajectory, universal feature these is functional deterioration nervous system concomitant apoptosis. Ferroptosis an (Fe)-dependent form programmed cell death that has been implicated pathogenesis conditions. It intricately associated intracellular Fe metabolism lipid homeostasis. The observed variety neurodegenerative diseases linked to etiology progression, although its precise role pathologies yet be elucidated. This review aims elucidate characteristics regulatory mechanisms ferroptosis, association diseases, recent advances ferroptosis-targeted therapeutic strategies. may therefore critical area for future research into diseases.

Language: Английский

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Pervasive Expostulation of p53 Gene Promoting the Precipitation of Neurogenic Convulsions: A Journey in Therapeutic Advancements

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 983, P. 176990 - 176990

Published: Sept. 7, 2024

Language: Английский

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Modulatory Impact of Oxidative Stress on Action Potentials in Pathophysiological States: A Comprehensive Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1172 - 1172

Published: Sept. 26, 2024

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and body's antioxidant defenses, significantly affects cellular function viability. It plays a pivotal role in modulating membrane potentials, particularly action potentials (APs), essential for properly functioning excitable cells such as neurons, smooth muscles, pancreatic beta cells, myocytes. The interaction oxidative stress AP dynamics is crucial understanding pathophysiology various conditions, including neurodegenerative diseases, cardiac arrhythmias, ischemia-reperfusion injuries. This review explores how influences APs, focusing on alterations ion channel biophysics, gap junction, calcium dynamics, mitochondria, Interstitial Cells Cajal functions. By integrating current research, we aim to elucidate contributes disease progression discuss potential therapeutic interventions targeting this interaction.

Language: Английский

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Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy

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

Published: Dec. 3, 2024

ABSTRACT Osteoarthritis (OA) is a chronic, degenerative joint disease primarily characterised by damage to the articular cartilage, synovitis and persistent pain, has become one of most common diseases worldwide. In OA various forms cell death have been identified, including apoptosis, necroptosis autophagic death. Ever‐growing observations indicate that ferroptosis, newly‐discovered iron‐dependent form regulated death, detrimental occurrence progression. this review, we first analyse pathogenetic mechanisms which iron overload, inflammatory response mechanical stress contribute ferroptosis. We then discuss how ferroptosis exacerbates progression, focusing on its impact chondrocyte viability, synoviocyte populations extracellular matrix integrity. Finally, highlight several potential therapeutic strategies targeting could be explored for treatment OA.

Language: Английский

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Inhibition of calpain reduces oxidative stress and attenuates pyroptosis and ferroptosis in Clostridium perfringens Beta-1 toxin-induced macrophages

Microbiological Research, Journal Year: 2024, Volume and Issue: 289, P. 127916 - 127916

Published: Sept. 27, 2024

Language: Английский

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Lipid metabolism: Novel approaches for managing idiopathic epilepsy

Neuropeptides, Journal Year: 2024, Volume and Issue: 108, P. 102475 - 102475

Published: Sept. 30, 2024

Language: Английский

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