Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury. TRPV1 activation has been associated to chronic inflammatory pain and peripheral neuropathy. Its expression is also detected in nonneuronal areas such as bladder, lungs, and cochlea where TRPV1 activation is responsible for pathology development of cystitis, asthma, and hearing loss. This review offers a comprehensive overview about TRPV1 receptor in the pathophysiology of chronic pain, epilepsy, cough, bladder disorders, diabetes, obesity, and hearing loss, highlighting how drug development targeting this channel could have a clinical therapeutic potential. Furthermore, it summarizes the advances of medicinal chemistry research leading to the identification of highly selective TRPV1 antagonists and their analysis of structure-activity relationships (SARs) focusing on new strategies to target this channel.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/med.21427 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cinnamic acid conjugated with triazole acetamides as anti-Alzheimer and anti-melanogenesis candidates: an in vitro and in silico study.
Sci Rep
January 2025
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
In this study, new cinnamic acid linked to triazole acetamide derivatives was synthesized and evaluated for anti-Alzheimer and anti-melanogenesis activities. The structural elucidation of all analogs was performed using different analytical techniques, including H-NMR, C-NMR, mass spectrometry, and IR spectroscopy. The synthesized compounds were assessed in vitro for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase enzymes.
View Article and Find Full Text PDFCrocin and gallic acid attenuate ethanol-induced mitochondrial dysfunction via suppression of ROS formation and inhibition of mitochondrial swelling in pancreatic mitochondria.
Mol Cell Biochem
January 2025
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Chronic/heavy exposure with ethanol is associated with risk of type 2 diabetes, due to β-cells dysfunction. It has been reported that ethanol can induce oxidative stress directly or indirectly by involvement of mitochondria. We aimed to explore the protective effects of the crocin/gallic acid/L-alliin as natural antioxidants separately on ethanol-induced mitochondrial damage.
View Article and Find Full Text PDFEffects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.
Drug Deliv Transl Res
January 2025
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.
View Article and Find Full Text PDFUnveiling the mechanism of action of a novel natural dual inhibitor of SARS-CoV-2 Mpro and PLpro with molecular dynamics simulations.
Nat Prod Bioprospect
January 2025
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
In the twenty-first century, we have witnessed multiple coronavirus pandemics. Despite declining SARS-CoV-2 cases, continued research remains vital. We report the discovery of sydowiol B, a natural product, as a dual inhibitor of SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro).
View Article and Find Full Text PDFATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage.
Nat Struct Mol Biol
January 2025
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA.
DNA damage in cells induces the expression of inflammatory genes. However, the mechanism by which cells initiate an innate immune response in the presence of DNA lesions blocking transcription remains unknown. Here we find that genotoxic stresses lead to an acute activation of the transcription factor NF-κB through two distinct pathways, each triggered by different types of DNA lesions and coordinated by either ataxia-telangiectasia mutated (ATM) or IRAK1 kinases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!