GPX4, ferroptosis, and diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

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Implication of lncRNA MSTRG.81401 in Hippocampal Pyroptosis Induced by P2X7 Receptor in Type 2 Diabetic Rats with Neuropathic Pain Combined with Depression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1186 - 1186

Published: Jan. 18, 2024

Major depressive disorder (MDD) is a common complication of diabetes and often observed alongside diabetic neuropathic pain (DNP) as comorbidity in patients. Long non-coding RNA (lncRNA) plays an important role various pathophysiological processes. The P2X7 receptor responsible for triggering inflammatory responses, such pyroptosis, linked to depression. aim this study was investigate the effect lncRNA MSTRG.81401 on hippocampal pyroptosis induced by rats with DNP combined MDD (DNP + MDD). Our results showed that expression significantly elevated hippocampus compared control group. Following administration shRNA targeting MSTRG.81401, notable elevation mechanical thermal thresholds comorbid MDD. Additionally, significant improvements depression-like behaviors were evident open-field test (OFT), sucrose preference (SPT), forced swim (FST). In rats, levels mRNA protein observed, along increased co-expression astrocytic marker glial fibrillary acidic (GFAP). Meanwhile, heightened NOD-like 3 (NLRP3), apoptosis-associated speck-like (ASC), pyroptosis-related Gasdermin D (GSDMD), caspase-1, IL-1β, IL-18, TNF-α detected, addition serum IL-18 TNF-α. After treatment above abnormal changes indicators inflammation improved. Therefore, our demonstrates can alleviate associated inhibiting receptor-mediated pathway pro-inflammatory responses. This suggests P2X7R/NLRP3/caspase-1 implicated scenario may serve potential target management diabetes.

Language: Английский

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Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Brain Sciences, Journal Year: 2023, Volume and Issue: 14(1), P. 19 - 19

Published: Dec. 23, 2023

The term “neuroinflammation” defines the typical inflammatory response of brain closely related to onset many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through efforts research. Consequently, new cellular molecular mechanisms, diverse conventional, emerging. In listing some those that will be subject our description discussion, essential important roles peripheral infiltrated monocytes clonotypic cells, alterations in gut–brain axis, dysregulation apelinergic system, endothelial glycocalyx component neuronal vascular units, variations expression genes levels encoding molecules by action microRNAs (miRNAs), or other epigenetic factors distinctive transcriptional factors, as role autophagy, ferroptosis, sex differences, modifications circadian cycle. Such can add significantly understanding complex etiological puzzle neuroinflammation ND. addition, they could represent biomarkers targets ND, which increasing elderly.

Language: Английский

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TRIM28 Fosters Microglia Ferroptosis via Autophagy Modulation to Enhance Neuropathic Pain and Neuroinflammation

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(11), P. 9459 - 9477

Published: April 22, 2024

Language: Английский

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New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6716 - 6716

Published: June 18, 2024

Neuropathic pain, which refers to pain caused by a lesion or disease of the somatosensory system, represents wide variety peripheral central disorders. Treating neuropathic is quite demanding, primarily because its intricate underlying etiological mechanisms. The nervous system relies on microglia maintain balance, as they are associated with serving primary immune responses in brain next cell communication. Ferroptosis, driven phospholipid peroxidation and regulated iron, vital mechanism death regulation. Neuroinflammation can be triggered ferroptosis microglia, contributes release inflammatory cytokines. Conversely, neuroinflammation induce iron accumulation resulting microglial ferroptosis. Accumulating evidence suggests that neuroinflammation, characterized glial activation substances, significantly exacerbates development pain. By inhibiting ferroptosis, it may possible prevent subsequently alleviate homopentameric α7 subtype neuronal nicotinic acetylcholine receptor (α7nAChR) has potential suppress activation, transitioning M1 an M2 phenotype, facilitating anti-inflammatory factors, ultimately reducing Recent years have witnessed growing recognition regulatory role α7nAChR could target for treating This review summarizes mechanisms related progress according recent research. Such exploration will help elucidate relationship between α7nAChR, provide new insights into management.

Language: Английский

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Mitophagy in Cell Death Regulation: Insights into Mechanisms and Disease Implications

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1270 - 1270

Published: Oct. 9, 2024

Mitophagy, a selective form of autophagy, plays crucial role in maintaining optimal mitochondrial populations, normal function, and intracellular homeostasis by monitoring removing damaged or excess mitochondria. Furthermore, mitophagy promotes degradation via the lysosomal pathway, not only eliminates mitochondria but also regulates programmed cell death-associated genes, thus preventing death. The interaction between various forms death has recently gained increasing attention relation to pathogenesis clinical diseases, such as cancers osteoarthritis, neurodegenerative, cardiovascular, renal diseases. However, despite abundant literature on this subject, there is lack understanding regarding In review, we discuss main pathways mitophagy, those related mechanisms (including apoptosis, ferroptosis, pyroptosis), relationship uncovered recent years. Our study offers potential directions for therapeutic intervention disease diagnosis, contributes molecular mechanism mitophagy.

Language: Английский

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Prediction and validation of anoikis-related genes in neuropathic pain using machine learning

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0314773 - e0314773

Published: Feb. 27, 2025

Background Neuropathic pain (NP) can be induced by a variety of clinical conditions, such as spinal cord injury, lumbar disc herniation (LDH), stenosis, diabetes, herpes zoster, and tumors, inflammatory stimuli. The pathogenesis NP is extremely complex. Specifically, in LDH, the herniated nucleus pulposus exerts mechanical pressure on nerve roots, triggering local inflammation consequent NP. Anoikis, special form programmed cell death, closely related to progression In this study, we sought clarify molecular characteristics anoikis-related genes NP, providing novel insights for diagnosis treatment Methods We screened NP-related based GSE124272 dataset obtained 439 from GeneCards database. Through Least Absolute Shrinkage Selection Operator (LASSO) Support Vector Machine (SVM) machine learning algorithms, six key hub were identified: hepatocyte growth factor ( HGF ), matrix metalloproteinase 13 MMP13 c-abl oncogene 1, non-receptor tyrosine kinase ABL1 elastase neutrophil expressed ELANE fatty acid synthase FASN long non-coding RNA Linc00324 ). Functional enrichment analyses, including Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG), alongside Set Enrichment Analysis (GSEA) immune infiltration analysis, performed these genes. Additionally, transcription factors potential therapeutic drugs predicted. also used rats construct an model validated analyzed using hematoxylin eosin (H&E) staining, real-time polymerase chain reaction (PCR), Western blotting assays. Results Our data indicated that have diagnostic value patients, confirmed experimental results. Moreover, study elucidated role during identified targeting Conclusion This further explores provides certain reference developing targeted strategies, thereby improving management.

Language: Английский

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Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3835 - 3835

Published: April 18, 2025

Chronic pain is an extremely prevalent healthcare issue that has a profound impact on individuals and society. Sex sex hormones regulate the threshold differently in males females processing. However, regulatory mechanisms of differences response to painful stimuli are still unclear, which contributes difficulty analgesic drug development. Interleukins mediate neuroinflammation involved development chronic pain. Recent studies have found regulation thresholds by interleukins. Most previous used male animals study effects treatments due complexity estrogen. This review summarizes only female or both sexes examine interleukin-regulated pain, provide theoretical basis for more targeted precision medicines

Language: Английский

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Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Published: Nov. 27, 2023

With the term neuroinflammation has defined typical inflammatory response of brain closely related to onset many neurological diseases. Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Currently, some progress been achieved through efforts research. Consequently, new cellular molecular mecha-nisms, diverse from conventional ones, emerging. In listing those that will be sub-ject our description discussion, essential important role peripheral infiltrated monocytes clonotypic cells, alterations in gut/brain axis, dysregulation apelinergic sys-tem, as changes endothelial glycocalyx blood-brain barrier, variation expres-sion genes levels encoding molecules by microRNAs (miRNAs), or other epige-netic factors distinctive transcriptional factors, autophagy, ferroptosis, sex differences modifications circadian cycle. Such mentioned can add significant pieces understanding complex etiological puzzle neuroinflammation. addi-tion, they could represent biomarkers targets neurodegenerative diseases, increase old populations.

Language: Английский

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A comprehensive review of traditional Chinese medicine in treating neuropathic pain

Heliyon, Journal Year: 2024, Volume and Issue: 10(17), P. e37350 - e37350

Published: Sept. 1, 2024

Neuropathic pain (NP) is a common, intractable chronic caused by nerve dysfunction and primary lesion of the nervous system. The etiology pathogenesis NP have not yet been clarified, so there lack precise effective clinical treatments. In recent years, traditional Chinese medicine (TCM) has shown increasing advantages in alleviating NP. Our review aimed to define therapeutic effect TCM (including prescriptions, extracts natural products from TCM) on reveal underlying mechanisms. Literature 2018 2024 was collected databases including Web Science, PubMed, ScienceDirect, Google academic CNKI databases. Herbal medicine, Traditional medicines (TCM), neuropathic pain, neuralgia peripheral neuropathy were used as search terms. anti-NP activity clarified propose strategies for discovering active compounds against NP, provide reference screen drugs TCM. We concluded that characteristics multi-level, multi-component, multi-target multi-pathway, which can alleviate through various pathways such anti-inflammation, anti-oxidant, anti-apoptotic pathway, regulating autophagy, intestinal flora, influencing ion channels. Based experimental study mechanism TCM, this paper offer analytical evidence support effectiveness treating These references will be helpful research development innovative with multiple levels targets. an treatment serve treasure house new drug development.

Language: Английский

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