Ion channel expression in intrinsic cardiac neurons: new players in cardiac channelopathies?

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: 1872(6), P. 119983 - 119983

Published: May 8, 2025

The autonomic nervous system is an important modulator of electrical disorders observed in cardiac pathologies through changes the balance between sympathetic and parasympathetic tone. final common pathway for neuronal control resides intrinsic (ICNS), composed intracardiac neurons (ICN), which allows sympathetic-parasympathetic efferent interactions at sites. ICNS a complex that plays crucial role regulation physiological parameters has been shown to contribute diseases, particular arrhythmias. It therefore understand molecular determinants, such as ion channels, excitability their potential modulation pathological conditions. This review discusses several channels expressed by ICN, including potassium (e.g., inward rectifier, calcium-dependent, voltage-activated, muscarinic-sensitive), voltage-gated sodium (VGSC), calcium (VGCC), hyperpolarization-activated cyclic nucleotide-gated (HCN) Transient Receptor Potential (TRP) Channels, involvement pathologies. We highlight need further research on ICN particularly under conditions, develop therapies

Language: Английский

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TRP Channels in Excitotoxicity

The Neuroscientist, Journal Year: 2024, Volume and Issue: unknown

Published: April 29, 2024

Glutamate excitotoxicity is a central mechanism contributing to cellular dysfunction and death in various neurological disorders diseases, such as stroke, traumatic brain injury, epilepsy, schizophrenia, addiction, mood disorders, Huntington's disease, Alzheimer's Parkinson's multiple sclerosis, pathologic pain, even normal aging-related changes. This detrimental effect emerges from glutamate binding receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Language: Английский

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Dementia and neurodegenerative diseases: What is known and what is promising at the cellular and molecular level

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Millions of people worldwide are affected by neurodegenerative diseases and cognitive impairment, which includes dementia, while there only symptomatic treatments available for this syndrome at present. However, several important prospective drug targets have been identified in recent years that can potentially arrest or even reverse the progression diseases. Their natural synthetic ligands currently experimental stage development. In vitro preclinical (e.g. using animal models) studies confirm their therapeutic potential, but clinical trials often fail produce conflicting results. Here, we first review complexity typology followed discussion treatments, and, finally, some novel molecular cellular approaches to problem.

Language: Английский

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Transient Receptor Potential Channels in the Healthy and Diseased Blood–Brain Barrier

Journal of Histochemistry & Cytochemistry, Journal Year: 2024, Volume and Issue: 72(4), P. 199 - 231

Published: April 1, 2024

The large family of transient receptor potential (TRP) channels are integral membrane proteins that function as environmental sensors and act ion after activation by mechanical (touch), physical (heat, pain), chemical stimuli (pungent compounds such capsaicin). Most TRP localized in the plasma cells but some them membranes organelles intracellular Ca 2+ -ion channels. involved neurological disorders their precise role(s) relevance these not clear. Endothelial blood–brain barrier (BBB) express vanilloid 1–4 thermal detection regulating BBB permeability. In disorders, responsible for edema formation brain. Therefore, drug design to modulate locally activity is a hot topic. Today, application channel antagonists against still limited.

Language: Английский

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Exploring therapeutic potential: Targeting TRPM7 in neurodegenerative diseases

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113142 - 113142

Published: Sept. 17, 2024

Language: Английский

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TRPV4 Channel Modulators as Potential Drug Candidates for Cystic Fibrosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10551 - 10551

Published: Sept. 30, 2024

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic transmembrane conductance regulator (CFTR) gene, resulting defective chloride ion channels. This leads to thick, dehydrated mucus that severely disrupts mucociliary clearance respiratory system and triggers infection eventually cause of death CF patients. Current therapeutic strategies primarily focus on restoring CFTR function, blocking epithelial sodium channels prevent dehydration, or directly targeting reduce its viscosity. Among expressed ciliated bronchial cells, transient receptor potential vanilloid 4 (TRPV4) channel emerges as significant pathogenesis. Activation TRPV4 affects regulation airway surface liquid modulating absorption intracellular calcium levels, which indirectly influences activity. also involved regulatory volume decrease (RVD) process enhances inflammatory responses Here, we combine current findings modulation promising approach for CF. Although limited studies have explored CF, emerging evidence indicates activation can significantly impact key pathological processes disease. Further investigation into modulators could lead innovative treatments alleviate severe complications improve outcomes

Language: Английский

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Epigenetic Control of Hyperuricemia and Gout by Gene Writer DNMT1 and RNA Editor ADAR1: Mechanism of Gout and Amyloid Dissolution in Down Syndrome

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Abstract Although DNA methyltransferase 1 (DNMT1) and RNA editor; ADAR triplications exist in Down syndrome (DS), their specific roles remain unclear. DNMT methylates DNA, yielding S-adenosine homocysteine (SAH), subsequently converted to (Hcy) adenosine by hydrolase (SAHH). converts inosine uric acid. We hypothesized that targeting epigenetic regulators editor, inhibiting Hcy adenosine, could alleviate DS phenotype including the congenital heart disease (CHD). wild type mice were treated with epigallocatechin gallate (EG), inhibitor of adenosine. Specific substrate gel zymography identified matrix metalloproteinases (MMPs)/A Disintegrin Metalloproteinase Thrombospondin motifs (ADAMTS) activities MMP12/ADAMTS12 MMP13/ADAMTS13 levels assessed via zymography. Cardiac DNMT1, ADAR, tissue metalloproteinase (TIMP1), SAHH, ten eleven translocator (TET2); hydroxy methylation; a gene eraser was measured. Calcium urate deposits suggested gout mechanism DS. Robust amyloid fibers mouse brain cortex most likely dissolved ADAMTS as its elevated tissues, corresponding decrease TIMP1 EG group. It appears triplication down cell adhesion molecule (DSCAM) (CAM1) fragment also help dissolve fibers, thus suggesting ADAMTS13/TIMP1 ratio predict plaque dissolution. Our results indicate cystathionine-β synthase (CBS) potential therapy for

Language: Английский

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Neuropathology of Neurological Disorders

Published: Jan. 1, 2024

Neuropathology delineates the examination of cells and tissues, to assimilate structure function neurological system as well diagnosis pathology diseases that impact nervous system. It studies effects disease on can be used diagnose categorize particular conditions. This comprises muscles, nerves, ganglia (the peripheral system), brain spinal cord central system). A wide array techniques such immunohistochemistry, molecular biology, light electron microscopy are being observe neuropathological alterations in various disorders. highlights structural functional observations ranging from cellular micro-anatomical constructs identify biomarkers responsible for progression diseases. Several imaging technologies also which include CT scans MRI deeply examine modifications The several disorders, Alzheimer's disease, Parkinson's Huntington's multiple sclerosis, rests severely neuropathology. In this chapter, we will discuss about neuropathology

Language: Английский

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Novel characterization of endogenous transient receptor potential melastatin 3 ion channels from Gulf War Illness participants

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(6), P. e0305704 - e0305704

Published: June 25, 2024

Gulf War Illness (GWI) is a chronic condition characterized by multisystem symptoms that still affect up to one-third of veterans who engaged in combat the three decades ago. The aetiology GWI mainly explained exposure multiple toxic agents, vaccines, and medications. As there significant overlap between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), objective this study was investigate biomarker widely reported Natural Killer (NK) cells from ME/CFS patients, Transient Receptor Potential Melastatin 3 (TRPM3) ion channel. NK 6 healthy controls (HC) participants were isolated, TRPM3 function assessed through whole-cell patch-clamp. demonstrated prior studies, HC expressed typical after pharmacomodulation. In contrast, pilot investigation demonstrates dysfunctional application agonist confirmed antagonist. There reduction than results measured HC. This provides an unprecedented research field involvement TRP channels pathomechanism potential medical interventions improve quality life.

Language: Английский

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TRP channels as potential target molecules for pharmacotherapy of neurological diseases

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 421 - 455

Published: Jan. 1, 2024

Language: Английский

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