scholarly journals Identification of Potential Human Ryanodine Receptor 1 Agonists and Molecular Mechanisms of Natural Small-Molecule Phenols as Anxiolytics

ACS Omega ◽  
2021 ◽  
Author(s):  
Yahong Chen ◽  
Xiaohong Wang ◽  
Haifeng Zhai ◽  
Yanling Zhang ◽  
Jianmei Huang
Keyword(s):  
Ryanodine Receptor ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Ryanodine Receptor 1

Identification of Four Key Biomarkers and Small Molecule Drugs Innasopharyngeal Carcinoma by Weighted Gene Co-expression Network Analysis

2020 ◽  
Author(s):  
Xi Pan ◽  
Jian-Hao Liu
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Tumor Stage ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Therapeutic Goals ◽  
Small Molecule Drugs

Abstract Background Nasopharyngeal carcinoma (NPC) is a heterogeneous carcinoma that the underlying molecular mechanisms involved in the tumor initiation, progression, and migration are largely unclear. The purpose of the present study was to identify key biomarkers and small-molecule drugs for NPC screening, diagnosis, and therapy via gene expression profile analysis. Methods Raw microarray data of NPC were retrieved from the Gene Expression Omnibus (GEO) database and analyzed to screen out the potential differentially expressed genes (DEGs). The key modules associated with histology grade and tumor stage was identified by using weighted correlation network analysis (WGCNA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of genes in the key module were performed to identify potential mechanisms. Candidate hub genes were obtained, which based on the criteria of module membership (MM) and high connectivity. Then we used receiver operating characteristic (ROC) curve to evaluate the diagnostic value of hub genes. The Connectivity map database was further used to screen out small-molecule drugs of hub genes. Results A total of 430 DEGs were identified based on two GEO datasets. The green gene module was considered as key module for the tumor stage of NPC via WGCNA analysis. The results of functional enrichment analysis revealed that genes in the green module were enriched in regulation of cell cycle, p53 signaling pathway, cell part morphogenesis. Furthermore, four DEGs-related hub genes in the green module were considered as the final hub genes. Then ROC revealed that the final four hub genes presented with high areas under the curve, suggesting these hub genes may be diagnostic biomarkers for NPC. Meanwhile, we screened out several small-molecule drugs that have provided potentially therapeutic goals for NPC. Conclusions Our research identified four potential prognostic biomarkers and several candidate small-molecule drugs for NPC, which may contribute to the new insights for NPC therapy.

Ryanodine Receptor 1 and Associated Pathologies

2013 ◽  
pp. 167-187 ◽  
Author(s):  
Julien Fauré ◽  
Joël Lunardi ◽  
Nicole Monnier ◽  
Isabelle Marty
Keyword(s):  
Ryanodine Receptor ◽  
Ryanodine Receptor 1

Unravelling the mechanisms underpinning chemokine receptor activation and blockade by small molecules: a fine line between agonism and antagonism?

2007 ◽  
Vol 35 (4) ◽  
pp. 755-759 ◽  
Author(s):  
E. Wise ◽  
J.E. Pease
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
G Protein Coupled Receptors ◽  
Considerable Effort ◽  
G Protein Coupled ◽  
Migration Of Cells

Chemokines are a family of small basic proteins which induce the directed migration of cells, notably leucocytes, by binding to specific GPCRs (G-protein-coupled receptors). Both chemokines and their receptors have been implicated in a host of clinically important diseases, leading to the notion that antagonism of the chemokine–chemokine receptor network may be therapeutically advantageous. Consequently, considerable effort has been put into the development of small-molecule antagonists of chemokine receptors and several such compounds have been described in the literature. One curious by-product of this activity has been the description of several small-molecule agonists of the receptors, which are typically discovered following the optimization of lead antagonists. In this review we discuss these findings and conclude that these small-molecule agonists might be exploited to further our understanding of the molecular mechanisms by which chemokine receptors are activated.

Maintaining the permeability barrier during protein trafficking at the endoplasmic reticulum membrane

2003 ◽  
Vol 31 (6) ◽  
pp. 1227-1231 ◽  
Author(s):  
A.E. Johnson
Keyword(s):  
Endoplasmic Reticulum ◽  
Small Molecule ◽  
Protein Trafficking ◽  
Molecular Mechanisms ◽  
Protein Translocation ◽  
Cellular Membrane ◽  
Permeability Barrier ◽  
Endoplasmic Reticulum Membrane ◽  
Ion Diffusion

Many proteins are translocated across or integrated into a cellular membrane without disrupting its integrity, although it is difficult to imagine how such macromolecular transmembrane movement can occur without simultaneously allowing significant small-molecule and ion diffusion across the bilayer. Recent studies have identified some molecular mechanisms that are involved in maintaining the permeability barrier of the endoplasmic reticulum membrane during co-translational protein translocation and integration. These mechanisms are both simple and direct in concept, but are operationally complex and require the co-ordinated and regulated interaction of several multicomponent complexes.

Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia

2004 ◽  
Vol 30 (3) ◽  
pp. 356-365 ◽  
Author(s):  
Monica Aleman ◽  
Joyce Riehl ◽  
Brian M. Aldridge ◽  
Richard A. Lecouteur ◽  
Jeffrey L. Stott ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Ryanodine Receptor 1

scholarly journals Malignant hyperthermia mutation sites in the Leu2442–Pro2477 (DP4) region of RyR1 (ryanodine receptor 1) are clustered in a structurally and functionally definable area

2006 ◽  
Vol 401 (1) ◽  
pp. 333-339 ◽  
Author(s):  
Mark L. Bannister ◽  
Tomoyo Hamada ◽  
Takashi Murayama ◽  
Peta J. Harvey ◽  
Marco G. Casarotto ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Structural Studies ◽  
Amino Acid Residues ◽  
Domain Interaction ◽  
Closed State ◽  
Interdomain Interaction ◽  
Ryanodine Receptor 1 ◽  
Domain Peptide ◽  
Interdomain Interactions

To explain the mechanism of pathogenesis of channel disorder in MH (malignant hyperthermia), we have proposed a model in which tight interactions between the N-terminal and central domains of RyR1 (ryanodine receptor 1) stabilize the closed state of the channel, but mutation in these domains weakens the interdomain interaction and destabilizes the channel. DP4 (domain peptide 4), a peptide corresponding to residues Leu2442–Pro2477 of the central domain, also weakens the domain interaction and produces MH-like channel destabilization, whereas an MH mutation (R2458C) in DP4 abolishes these effects. Thus DP4 and its mutants serve as excellent tools for structure–function studies. Other MH mutations have been reported in the literature involving three other amino acid residues in the DP4 region (Arg2452, Ile2453 and Arg2454). In the present paper we investigated the activity of several mutants of DP4 at these three residues. The ability to activate ryanodine binding or to effect Ca2+ release was severely diminished for each of the MH mutants. Other substitutions were less effective. Structural studies, using NMR analysis, revealed that the peptide has two α-helical regions. It is apparent that the MH mutations are clustered at the C-terminal end of the first helix. The data in the present paper indicates that mutation of residues in this region disrupts the interdomain interactions that stabilize the closed state of the channel.

scholarly journals Functional Characterization of C-terminal Ryanodine Receptor 1 Variants Associated with Central Core Disease or Malignant Hyperthermia

2017 ◽  
Vol 4 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Remai Parker ◽  
Anja H. Schiemann ◽  
Elaine Langton ◽  
Terasa Bulger ◽  
Neil Pollock ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Functional Characterization ◽  
Central Core ◽  
Central Core Disease ◽  
Ryanodine Receptor 1
Sign in / Sign up

Export Citation Format

Share Document