Receptors & Clinical Investigation (E-Journal - Smart Science & Technology)
Not a member yet
168 research outputs found
Sort by
Computational Characterization of Afucosylation-Based IgG1 Heterogeneity
Get PDFIgG1s produced by cell culture are heterogeneous with respect to their afucosylated Fc glycan content. Since afucosylation content dramatically changes the nature of IgG1s, there exists a need for methods capable to dissecting the contributions of the different afucosylated IgG1 forms to biological activity. Recently, Zhan and Chung applied classical ligand-receptor mathematical analysis to receptor binding data obtained from heterogeneous mixtures of afucosylated IgG1s in order to develop methods capable of performing such operations [1]. By explaining important experimental observations and extracting valuable biochemical property information embedded in the data, their model provides a convincing demonstration of the role that mechanistic mathematical modeling can play in characterizing heterogeneous mixtures of complex molecules. This review highlights important features of their mathematical analysis from a drug development perspective
Transient Receptor Potential Vanilloid 1 in animal tissues: An overview to highlight similarities and differences with human species
Get PDFThe purpose of this review is to give an overview of the identification and the characterization of Transient Receptor Potential Vanilloid 1 (TRPV1) in animal tissues. TRPV1 is a receptor belonging to the superfamily of Transient Receptor potential (TRP) and it was first identified in dorsal root ganglion in 1997. After, the scientific interest on this receptor increased, and nowadays it is possible to read a huge bibliography dealing with this receptor that is considered ubiquitarian. Actually, it was identified in the majority of animal and human tissues in physiological and pathological conditions. The involvement of TRPV1 receptor is considered as a key to understand aetiopathogenic mechanisms and to try to find a therapeutic treatment. In spite of the deep knowledge on TRPV1 molecular structure, more studies are required to better understand the cascade following its activation. For all the previous mentioned reasons, TRPV1 was investigated in species of interest of Veterinary Medicine and some of them are important animal models for human medicine, especially for oncology and analgesic therapeutic strategies
GPR30 is a Potential Therapeutic Target in Human Carcinoma in situ and Seminomas
Get PDFThe G protein-coupled estrogen receptor (GPR30) is suggested to exert a role in non-nuclear estrogen signalling and is over-expressed in a variety of hormone dependent cancer entities. It is well established that oestrogens are involved in testicular germ cell tumours. In a recent paper published in Journal of Cellular Physiology, we show that down regulation of estrogen receptor ? (ER?) associates with GPR30 over-expression both in human testicular carcinoma in situ (CIS) and seminomas. In addition, we demonstrate that 17b-oestradiol induces the ERK1/2 activation through GPR30. The results suggested that exposure to oestrogens or oestrogen-mimics, in some as of yet undefined manner, diminishes the ERb-mediated growth restraint in CIS and in human testicular seminoma, indicating that GPR30 could be a potential therapeutic target to design specific inhibitors
Associations of sorLA/SORL1 with Alzheimer\u27s disease
Get PDFIn recent years Alzheimer’s disease (AD) has emerged as a research priority mainly due to an impressive increase in the average life expectancy in humans, which is associated with debilitating neurodegenerative disorders. The cardinal feature of the disease is accumulation of the amyloid-? peptide, which is derived from the sequential proteolytic cleavage of the amyloid precursor protein (APP). SorLA (sorting protein-related receptor with A-type repeats) is a member of the VPS10p-domain receptor gene family and identified as a significant sorting receptor that controls the processing and trafficking of APP. This review systematically discusses information on sorLA associations with AD including the mechanisms that regulate sorLA activity. We also describe how advances in understanding the mechanisms by which sorLA can reduce the amyloidogenic pathway may open for novel therapeutic strategies in tackling this devastating disorder
Role of Epidermal growth factor receptor in odontogenic epithelium and development of odontogenic lesions
Get PDFGrowth is a highly coordinated process which is sustained by several growth factors and apoptotic factors. Any disturbance in this delicate balance leads to pathologies and genes that have such potential to produce tumors when mutated are known as oncogenes. EGFR an important growth factor that is involved in several physiological processes is presently one of the most common genes in targeted cancer therapies. Though, its potential as an oncogene target in head and neck epithelial tumors like squamous cell carcinoma is gaining importance and opening doors to revolutionizing cancer treatment modalities, its role in other head and neck epithelia like odontogenic epithelia remains vague and needs attention. The present article highlights some of the key findings in our research evaluating the role of EGFR in physiologic odontogenic epithelium that is comprised within pericoronal follicles. The research involved study of immunohistochemical examination of 35 pericoronal follicles removed from patients with asymptomatic impacted tooth extractions. The follicles were assessed for intensity, percentage of staining and location of the EGFR stain. The follicles predominantly showed intense staining pattern and location of EGFR positivity in most epithelium and rests were combined both cytoplasmic and membrane positivity. These findings reemphasize the inherent proliferative potential present in follicles and their role in formation of odontogenic tumors like ameloblastomas in long term impacted teeth. The potential of EGFR as a treatment target in odontogenic tumors also remains plausible
Structural Motifs in the Extracellular Domain of the Prolactin Receptor Govern Fold and Functionality
Get PDFThe prolactin receptor (PRLR) is an archetype cytokine receptor. It is a single-pass transmembrane receptor with limited complexity that is devoid of enzyme activity. Intracellular signaling involves various receptor-associated kinases including Jak2, Erk1/2, Src and Akt. As the PRLR is emerging as a relevant target in Oncology the understanding of the molecular basis of its activation is crucial. In the frame of an inter-disciplinary consortium involving biophysicists, structural biologists and cell biologists, we have successfully combined complementary approaches such as optical and nuclear magnetic resonance spectroscopic analyses, X-ray crystallography, surface plasmon resonance and cell-based assays to start elucidate the structural features of ligand-receptor interaction. However, the features of the PRLR extracellular domain (ECD) that participate in the transmission of the hormonal message across the cell membrane and/or in selective activation of intracellular signaling cascades remained uncharacterized. In two recently published studies, we identified residues 146 and 170 as two key residues of the PRLR-ECD that control critical receptor properties including basal signaling activity, ligand sensitivity, species specificity, folding, stability and receptor turnover. These two residues are in close proximity of each other in the membrane proximal domain of the PRLR-ECD and participate in a network of interactions with other residues, in particular within a specific residue quartet. Strikingly, these residues are involved in, or close to, the receptor dimerization interface, suggesting that their mechanism of action may involve structural reorientation of the receptor chains that are necessary to (selectively) disseminate the signal from the ECD to the intracellular domain. The identification of such residues in this and other cytokine receptors should affect future structure-directed drug development strategies aimed at providing pathway-selective treatment strategies
G protein-coupled receptors for lysophosphatidylethanolamine
Get PDFLysophospholipids like lysophosphatidic acid (LPA) and sphingosine 1-phosphate have been intensively studied over the last several decades, and these studies have resulted in the identification of their G protein-coupled receptors (GPCR) and in the discoveries of new drugs targeting GPCRs. However, lysophosphatidylethanolamine (LPE) has not attracted much research attention. Recently, we found several interesting points regarding the action and signaling of LPE, that is, its cell-type dependence, structure specificity, and unique signaling. In particular, LPE signaling through LPA1 receptor (type 1 lysophosphatidic acid receptor) was found to be cell type dependent, and LPEs with different chain lengths induced different responses in different cells without LPA1 involvement. Here, we review recent findings and propose possible action modes of LPE GPCRs in different cells
Expression of nicotinic acetylcholine receptor subunits alpha 4, alpha 7 and beta 2 in human internal mammary arteries of non-smokers and smokers
Get PDFNicotinic acetylcholine receptors (nAChR) are widely expressed in non-neuronal tissue, but data about their expression in vascular tissue are rare. To study the expression of nAChR ?4, ?7 and ?2 in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in human arteries of smokers and non-smokers, arteriae thoracicae internae dissected for coronary artery bypass grafting were analysed immunhistochemically and by polymerase chain reaction (PCR). ECs of the tunica intima and the vasa vasorum as well as the VSMCs of the tunica media showed clear staining for nAChR ?4, ?7 and ?2, without significant differences between non-smokers and smokers in all vascular layers. Further verification of nAChR ?4, ?7 and ?2 expression of whole-tissue homogenates using PCR analysis showed no differences in the subtype expression between non-smokers and smokers. This provides an important basis for further investigations using positron electron tomography (PET) tracers for imaging of nAChRs in vascular health and disease
Acetylcholine receptors antibodies in postural tachycardia syndrome
Get PDFPostural tachycardia syndrome (POTS) is a type of chronic orthostatic intolerance. Acetylcholine receptor antibodies (AChR-ab) mediated autonomic dysfunction is common in POTS patients. Therefore, it is important to explore the value of serum AChR-ab in those patients. In a recent paper published in Pediatric Cardiology, we compared POTS patients with different AChR-ab status and found preceding infection, syncope and fatigue as main clinical features of POTS patients with AChR-ab positive. Thus, clinicians can determine targeted therapy of acetylcholinesterase inhibitors or immunotherapy according to both the specific clinical features and the results of AChR-ab detecting
ATP Binding and Channel Activation in P2X Receptors
Get PDFPurinergic P2X receptors are a family of nonselective cation channels gated by extracellular adenosine 5?-triphosphate. They are important drug targets primarily because of their involvement in neuropathic pain and inflammation. ATP binds allows Na+ and Ca2+ to pass through the channel pore, thus causing membrane depolarization and a?ecting various downstream Ca2+-dependent signaling processes. A concerted effort by investigators over the last two decades has culminated in significant advances in our understanding of where ATP binds and how ATP binding leads to channel opening and ion flux. The recent publication of the crystal structures for both the closed and open channel conformations of the zebrafish P2X4 receptor sheds new light on how P2X receptors work. In this review, we will attempt to present the existing functional data regarding ATP binding with the available crystal structure data and different experimental approaches that have been used to explore the ATP-binding sites