September 2022 "Systemic sclerosis (SSc) is a systemic autoimmune disease with the key features of inflammation

The chemokine system exhibits great versatility, with more than 50 chemokines interacting with over 20 receptor-chemokine complexes and revealing the diverse and multifaceted nature of the chemokine receptor system study of all structures of CKRs characterizes the molecular recognition processes governing the CKR system experimental structures of chemokine receptors, which provide insights into the complexity of the chemokine system

September 2022 "The endocannabinoid system plays a key role in the intersection of the nervous, endocrine , and immune systems, regulating not only their functions but also how they interplay with each other cell wall, disrupt not only the hypothalamic–pituitary–adrenal axis but also affects other endocrine systems

cells expressing the chemokine receptor endogenously together with relevant enzymes and co-receptor systems our understanding on the dynamics and biological relevance of these PTMs in the chemokine receptor system which may ultimately allow for new precise targeting of the immune system.

Although they form an ancient signaling system, there is still a great deal of variety in neuropeptides By comparison, we found that the Releasing Hormone-Related Peptides (GnRHs) system of Sternorrhyncha Additionally, we discovered that the neuropeptide signaling systems of Sternorrhyncha were very different This research provides more knowledge on neuropeptide systems and sets the groundwork for the creation

August 2022 "Host response to infection involves the activation of the complement system leading to the

GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health of the physiological balance between healthy and pathological conditions; thus, their importance in systems The molecular diversity of GPCR signaling systems is likely to be closely associated with disease-associated compartmentalization, thus enabling a nuanced GPCR-based capacity to interdict multiple disease pathomechanisms at a systemic

October 2022 "Perturbation of the endocannabinoid system can have profound effects on immune function Microglia are one of few cell types with a self-contained endocannabinoid system and are positioned at the interface between the immune system and the central nervous system. Furthermore, we demonstrate that the efficacy of different synthetic cannabinoid treatments with respect degrade, and respond to cannabinoids which has implications for the development of cannabinoid-based treatments

September 2022 Dynamics of tumor-associated macrophages in a quantitative systems pharmacology model of immunotherapy in triple-negative breast cancer "Quantitative systems pharmacology (QSP) modeling is the dynamics of TAMs into our previously published QSP model to investigate their impact on cancer treatment

between antagonist, partial agonist, and biased agonist outcomes in various primary and clonal cell systems

Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and their Here, we generated a transcriptome of the central nervous system (CNS) of G. molesta.

August 2022 "The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans." Read more at the source #DrGPCR #GPCR #IndustryNews

schizophrenia-relevant brain circuits "Although the cannabinoid type-2 receptor (CB2) is highly expressed in the immune system emerging evidence points to CB2 playing a key role in regulating neuronal function in the central nervous system

September 2022 "Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various sensory modalities and relay negative valence to the lateral and central amygdala, respectively. Both CGRP populations and their amygdala projections are required for multi-sensory threat perception and aversive memory formation. The identification of unified innate threat pathways may provide insights into developing therapeutic candidates for innate fear-related disorders." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment KEGG pathway analysis highlighted the most significant pathways associated with depression treatment,

Therefore, mGluR2 and mGluR3 have been considered as potential drug targets for the treatment of many

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes mellitus is among the greatest concerns. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who are experiencing oxidative stress. Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein uncoupling." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses type 1 (HIV-1). We used TIRF microscopy and a statistical method to track and classify the motion of different receptor subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. " Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Successful prednisolone or calcimimetic treatment of acquired hypocalciuric hypercalcemia

Until recently, itch pathophysiology was poorly understood and treatments were poorly effective in relieving

June 2022 Neurocrine Biosciences Presents Data on Treatment of Adolescent Patients with Classic Congenital Substantial Reductions in Key Hormones and Hormone Precursors Observed After 14 Days of Crinecerfont Treatment The company also presented data highlighting patient preferences and treatment patterns in classic CAH

January 2022 ChemoCentryx Announces EU Approval of TAVNEOS® (avacopan) for the Treatment of ANCA-Associated approved within the European Union in combination with a rituximab or cyclophosphamide regimen for the treatment

April 2022 Addex Expands Pipeline With Selective M4 Positive Allosteric Modulator Program For The Treatment

March 2022 Confo Therapeutics Doses First Subjects In Phase 1 Clinical Trial Of CFTX-1554 For The Treatment CFTX-1554 is being developed as a non-opioid approach to the treatment of neuropathic pain, a debilitating condition caused by damage to the nerves outside of the brain and spinal cord, for which current treatment

April 2022 John Streicher talks about his work on terpenes found in cannabis as these may be a novel way to treat pain without the negative side effects " Many people are familiar with cannabis, but John Streicher , PhD, takes a closer look at the plant’s aromatic chemical compounds called terpenes. These compounds may be a novel way to treat pain without the negative side effects of cannabinoids or opioids." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but Not G Protein Interaction "The calcium-sensing receptor is a homodimeric class C G protein-coupled receptor (GPCR) that senses extracellular Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT) unit that activates G protein-dependent signaling via twin Cysteine-rich domains linked to transmembrane heptahelical (HH) bundles. It plays a key role in the regulation of human calcium and thus mineral metabolism. However, the nature of interactions between VFT units and HH bundles, and the impacts of heterozygous or homozygous inactivating mutations, which have implications for disorders of calcium metabolism are not yet clearly defined. Herein we generated CaSR-GABAB1 and CaSR-GABAB2 chimeras subject to GABAB -dependent endoplasmic reticulum sorting to traffic mutant heterodimers to the cell surface. Transfected HEK-293 cells were assessed for Ca2+o -stimulated Ca2+i mobilization using mutations in either the VFT domains and/or HH bundle intraloop-2 or intraloop-3. When the same mutation was present in both VFT domains of receptor dimers, analogous to homozygous neonatal severe hyperparathyroidism (NSHPT), receptor function was markedly impaired. Mutant heterodimers containing one wild-type (WT) and one mutant VFT domain, however, corresponding to heterozygous familial hypocalciuric hypercalcemia type-1 (FHH-1), supported maximal signaling with reduced Ca2+o potency. Thus two WT VFT domains were required for normal Ca2+o potency and there was a pronounced gene-dosage effect. In contrast, a single WT HH bundle was insufficient for maximal signaling and there was no functional difference between heterodimers in which the mutation was present in one or both intraloops; ie, no gene-dosage effect. Finally, we observed that the Ca2+o -stimulated CaSR operated exclusively via signaling in-trans and not via combined in-trans and in-cis signaling. We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)." Read more at the source #DrGPCR #GPCR #IndustryNews

Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social characterized by several important neurohormonal perturbations, emanating from both the autonomic nervous system This is why sympatholytic treatments (such as β-blockers) and renin-angiotensin system inhibitors or

The immune system depends on chemokines to direct cell migration during immune surveillance and inflammation However, an imbalance in the chemokine system can also contribute to various diseases, such as inflammatory glycosaminoglycans (GAGs) to regulate the movement of leukocytes throughout the body, ensuring a functional immune system Interestingly, in monocytes and dendritic cells exposed to treatments mimicking inflammation, CCR1, CCR2