Voltage-gated sodium channels in cancers

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: July 25, 2024

Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed a variety of cancers, derived from "non-excitable" tissues that do not generate classic potentials, showing potential as promising pharmacological target for cancer. Most the previous review articles on this topic limited scope, largely unable to provide researchers with comprehensive understanding role cancers. Here, we expression patterns all nine α-subunit (SCN1A-11A) their four regulatory β-subunit (SCN1B-4B). We reviewed data Cancer Genome Atlas (TCGA) database, complemented by an extensive search published papers. summarized independent studies analyzed TCGA database regarding impact A comparison between evidence gathered was performed scrutinize biases prior research insights into future directions. The supports view VGSCs play important diagnostics well therapeutics cancer types, such breast, colon, prostate, lung This paper provides overview current knowledge voltage-gated cancer, avenues further research. While is required fully understand clinical diagnosis treatment promising.

Language: Английский

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Synthetic peptide scaffolds as ion channels and molecular carriers

Current Opinion in Chemical Biology, Journal Year: 2025, Volume and Issue: 84, P. 102563 - 102563

Published: Jan. 7, 2025

Transmembrane ion exchange controls biological functions and is essential for life. Over the years, a great variety of nature-inspired artificial channels carriers have been synthesized to control promote across membranes. In this context, peptides emerged as ideal scaffolds synthetic due their biocompatibility, accessibility chemical versatility. Peptides already shown potential construction range transporters either alone or in combination with other molecular scaffolds. Among diversity peptide-based transporters, we can find key examples single-molecule supramolecular transmembrane ionophores. Peptide also found delivery biomolecular cargos such nucleic acids proteins. This review covers some most relevant advances transport field from last few years.

Language: Английский

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Noninvasive Imaging of Immune Cell Activity in Myocardial Infarction Phases Using ^99mTc-HYNIC-mAb_Kv1.3 SPECT/CT

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Acute myocardial infarction (MI) remains a leading cause of mortality worldwide, with inflammatory and reparative phases playing critical roles in disease progression. Currently, there is pressing need for vivo imaging techniques to monitor immune cell infiltration inflammation activity during these phases. We developed novel probe, 99mTc-HYNIC-mAbKv1.3, utilizing monoclonal antibody that targets the voltage-gated potassium channel 1.3 (Kv1.3). This probe enables visualization cells express high levels Kv1.3 proteins. In murine MI model, SPECT/CT 99mTc-HYNIC-mAbKv1.3 demonstrated specific uptake an infarcted myocardium phase, reflecting activity. During exhibited prolonged retention area, suggestive ongoing proliferation. Immunofluorescence staining confirmed probe's specificity. Biodistribution analysis indicated preferential accumulation liver, consistent findings. Combined [18F]FDG PET/CT, modalities provided comprehensive insights into viability inflammation. study highlights potential as noninvasive tool different MI, guide therapeutic interventions, predict Further translational studies are warranted explore its clinical applicability cardiac pathologies.

Language: Английский

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Discovery of therapeutic promising natural products to target Kv1.3 channel, a transmembrane protein regulating immune disorders, through multidimensional virtual screening, molecular dynamics simulations and biological validation

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142636 - 142636

Published: March 1, 2025

Language: Английский

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Pharmacological inhibition of Kv1.3 channel reduces sevoflurane-induced cognitive impairment through NLRP3-dependent microglial modulation

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111351 - 111351

Published: April 1, 2025

Language: Английский

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Detection of Voltage-Gated Potassium Channels 1.3 via Immuno-PET Visualizes Rheumatoid Arthritis

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Rheumatoid arthritis (RA) is a chronic inflammatory condition affecting approximately 1% of the global population, yet current diagnostic tools for early-stage RA lack sensitivity and fail to identify optimal treatment candidates. Voltage-gated potassium channel 1.3 (Kv1.3) plays crucial role in immune cell activation, particularly effector memory T lymphocytes macrophages, which drive inflammation active RA. This study aimed develop evaluate novel Kv1.3-targeted radiopharmaceutical, [68Ga]Ga-NOTA-anti-Kv1.3, precise monitoring quantification joint mouse model PET imaging revealed significantly higher radioactivity concentration inflamed joints compared normal at all time points, with peak uptake 11.73 %ID/g 4 h postinjection 1.55 noninflamed joints. Histological analysis confirmed presence macrophages tissues their high Kv1.3 expression. Additionally, tracer correlated strongly clinical scores (Pearson r = 0.8789, p < 0.0001), demonstrating probe's tracking progression. successfully developed 68Ga-labeled Kv1.3-targeting radiopharmaceutical that enables visualization arthritic joints, showing early diagnosis disease monitoring. approach offers potential guiding immune-targeted therapies assessing efficacy

Language: Английский

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Large-Scale AI-Based Structure and Activity Prediction Analysis of ShK Domain Peptides from Sea Anemones in the South China Sea

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(2), P. 85 - 85

Published: Feb. 16, 2025

Sea anemone peptides represent a valuable class of biomolecules in the marine toxin library due to their various structures and functions. Among these, ShK domain are particularly notable for selective inhibition Kv1.3 channel, holding great potential applications immune regulation treatment metabolic disorders. However, these peptides' structural complexity diversity have posed challenges functional prediction. In this study, we compared 36 from four species sea South China explored binding ability with channels by combining molecular docking dynamics simulation studies. Our findings highlight that variations loop length, residue composition, charge distribution among affect stability specificity. This work presents an efficient strategy large-scale peptide structure prediction activity screening, providing foundation future pharmacological research.

Language: Английский

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Voltage-gated potassium channels associated with head and neck cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(3), P. 189340 - 189340

Published: May 1, 2025

Language: Английский

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Therapeutic potential of voltage-dependent potassium channel subtype 1.3 blockade in alleviating macrophage-related renal inflammation and fibrogenesis

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: May 5, 2025

Language: Английский

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Electrophysiological and Molecular Docking Analysis of 1,8-Cineole's Effects on Potassium Currents in Mouse DRG Neurons

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151968 - 151968

Published: May 1, 2025

Language: Английский

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