Hydrocephalus is a serious condition that impacts patients of all ages. The standards of care are surgical options to divert, or inhibit production of, cerebrospinal fluid; to date, there are no effective pharmaceutical treatments, to our knowledge. The causes vary widely, but one commonality of this condition is aberrations in salt and fluid balance. We have used a genetic model of hydrocephalus to show that ventriculomegaly can be alleviated by inhibition of the transient receptor potential vanilloid 4, a channel that is activated by changes in osmotic balance, temperature, pressure and inflammatory mediators. The TRPV4 antagonists do not appear to have adverse effects on the overall health of the WT or hydrocephalic animals.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526552 | PMC |
| http://dx.doi.org/10.1172/jci.insight.137646 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structure- and Ligand-Based Virtual Screening for Identification of Novel TRPV4 Antagonists.
Molecules
December 2024
Structural Bioinformatics Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland.
Transient receptor potential vanilloid (TRPV) 4 is involved in signaling pathways specifically mediating pain and inflammation, making it a promising target for the treatment of various painful and inflammatory conditions. However, only one drug candidate targeting TRPV4 has entered the clinical trials. To identify potential TRPV4 inhibitors for drug development, we screened a library of ion channel-modulating compounds using both structure- and ligand-based virtual screening approaches.
View Article and Find Full Text PDFBackground: Aortic valve stenosis (AVS) is a progressive disease characterized by fibrosis, inflammation, calcification, and stiffening of the aortic valve leaflets, leading to disrupted blood flow. If untreated, AVS can progress to heart failure and death within 2 to 5 years. Uncovering the molecular mechanisms behind AVS is key for developing effective noninvasive therapies.
View Article and Find Full Text PDFTRPV4 stimulates colonic afferents through mucosal release of ATP and glutamate.
Br J Pharmacol
December 2024
Department of Pharmacology, University of Cambridge, Cambridge, UK.
Background And Purpose: Abdominal pain is a leading cause of morbidity for people living with gastrointestinal disease. Whereas the transient receptor potential vanilloid 4 (TRPV4) ion channel has been implicated in the pathogenesis of abdominal pain, the relative paucity of TRPV4 expression in colon-projecting sensory neurons suggests that non-neuronal cells may contribute to TRPV4-mediated nociceptor stimulation.
Experimental Approach: Changes in murine colonic afferent activity were examined using ex vivo electrophysiology in tissues with the gut mucosa present or removed.
The Role of the TRPV4 Channel in Intestinal Physiology and Pathology.
J Inflamm Res
November 2024
Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
The transient receptor potential vanilloid 4 channel (TRPV4) is an important member of the TRP superfamily of cation channels. The channel can be activated by different physical and chemical stimuli, such as heat, osmotic, and mechanical stress. It regulates the release of nociceptive peptides (substance P and calcitonin gene-related peptide), and mediates neurogenic inflammation, which indicates the involvement of TRPV4 as a nociceptor.
View Article and Find Full Text PDFTRPV4-mediated Mechanotransduction Regulates the Differentiation of Valvular Interstitial Cells to Myofibroblasts: Implications for Aortic Stenosis.
bioRxiv
November 2024
University of Maryland, Department of Nutrition and Food Science, College Park, MD 20742.
As aortic valve stenosis (AVS) progresses, the valve tissue also stiffens. This increase in tissue stiffness causes the valvular interstitial cells (VICs) to transform into myofibroblasts in response. VIC-to-myofibroblast differentiation is critically involved in the development of AVS.
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!