Neuropeptides, Год журнала: 2024, Номер 108, С. 102475 - 102475
Опубликована: Сен. 30, 2024
Язык: Английский
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 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.
Язык: Английский
Процитировано
1
Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(8)
Опубликована: Авг. 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.
Язык: Английский
Процитировано
3
Neurobiology of Disease, Год журнала: 2025, Номер 206, С. 106838 - 106838
Опубликована: Фев. 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.
Язык: Английский
Процитировано
0
Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 298, С. 118269 - 118269
Опубликована: Май 10, 2025
Язык: Английский
Процитировано
0
Molecular Biology Reports, Год журнала: 2025, Номер 52(1)
Опубликована: Май 20, 2025
Язык: Английский
Процитировано
0
Antioxidants, Год журнала: 2025, Номер 14(5), С. 613 - 613
Опубликована: Май 20, 2025
Emerging evidence links ferroptosis–mitochondrial dysregulation to depression pathogenesis through an oxidative stress–energy deficit–neuroinflammation cycle driven by iron overload. This study demonstrates that accumulation initiates ferroptosis via Fenton reaction-mediated lipid peroxidation, compromising neuronal membrane integrity and disabling the GPx4 antioxidant system. Concurrent mitochondrial complex I/IV dysfunction impairs ATP synthesis, creating AMPK/mTOR signaling imbalance calcium dyshomeostasis synergistically impair synaptic plasticity. Bidirectional crosstalk emerges: peroxidation derivatives oxidize cardiolipin, while ROS overproduction activates ACSL4 amplify ferroptotic susceptibility, forming a self-reinforcing neurodegenerative loop. Prefrontal–hippocampal metabolomics reveal paradoxical metabolic reprogramming with glycolytic compensation suppressing biogenesis (via PGC-1α/TFAM downregulation), trapping neurons in bioenergetic crisis. Clinical data further show microglial M1 polarization cGAS-STING activation sustains neuroinflammation IL-6/TNF-α release. We propose “ferroptosis–mitochondrial fragmentation–metabolic maladaptation” triad as mechanistic subtyping criteria for depression. Preclinical validation shows combinatorial therapy (iron chelators + SIRT3 agonists) rescues viability restoring energy flux. work shifts therapeutic paradigms from monoaminergic targets toward multimodal strategies addressing homeostasis, organelle dynamics, vulnerability—a framework significant implications developing neuroprotective antidepressants.
Язык: Английский
Процитировано
0
Journal of Pharmacy and Pharmacology, Год журнала: 2025, Номер unknown
Опубликована: Июнь 4, 2025
Cannabidiol (CBD) and 9-tetrahydrocannabinol (THC) are the two main components of cannabis that provide its therapeutic benefits. CBD has been extensively studied for role in reducing seizures, among many other uses. While exact mechanisms by which works to relieve seizures have not yet fully determined, it is evident effectively diminishes seizure activity now being used as an approved treatment severe forms non-responsive epilepsy. As essential several biological processes, microRNAs (miRNAs) crucial achieving optimal cellular functioning. During past few years, there increasing interest elucidating functional significance Yet, still considerable ambiguity regarding precise miRNAs involved disorders also their direct interaction with CBD. Herein, we seek present overview varying offers benefits concerning seizures. Accordingly, highlighted shared molecular targets between alleviating symptoms shed light on ways new diagnostic modalities could be shaped future.
Язык: Английский
Процитировано
0
Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер 175, С. 106242 - 106242
Опубликована: Июнь 3, 2025
Epilepsy is a neurological disorder affecting approximately 50 million people globally and characterised by recurrent, unprovoked seizures resulting from abnormal, excessive synchronised firing of neurons. Developing new therapeutic targets biomarkers key to improving the diagnosis, treatment, management. This scoping review examines current literature on preclinical clinical applications dietary interventions that target neurolipidome in epilepsy. Specifically, it investigates role lipids underlying pathogenesis A comprehensive search databases was conducted identify peer-reviewed articles published past ten years. Original research focusing both adult paediatric epilepsy disrupted lipid metabolism were included, total 101 papers. Our identified several implicated epilepsy, including sphingolipids, free fatty acids, endocannabinoids, cholesterol, triglycerides, phospholipids, also explores complex interactions between these their roles disease process. Furthermore, our study highlighted Ketogenic Diet (KD) Modified Atkins (MAD) have proven effective adjunctive or alternative treatments populations, patient quality life reducing seizure frequency. Additionally, treatment with lipid-based supplements, such as eicosapentaenoic acid, docosahexaenoic fish oil, cannabidiol, has been associated reduction rates patients drug-resistant In summary, findings this indicate KD MAD supplements are for managing paediatrics, adults, animal models. However, further necessary elucidate pathophysiological mechanisms development progression
Язык: Английский
Процитировано
0
European Journal of Pharmacology, Год журнала: 2024, Номер 983, С. 176990 - 176990
Опубликована: Сен. 7, 2024
Язык: Английский
Процитировано
2
Antioxidants, Год журнала: 2024, Номер 13(10), С. 1172 - 1172
Опубликована: Сен. 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.
Язык: Английский
Процитировано
2