Therapeutic Potentials of A2B Adenosine Receptor Ligands: Current Status and Perspectives

2019 ◽  
Vol 25 (25) ◽  
pp. 2741-2771 ◽  
Author(s):  
Balakumar Chandrasekaran ◽  
Sara Samarneh ◽  
Abdul Muttaleb Yousef Jaber ◽  
Ghadir Kassab ◽  
Nikhil Agrawal
Keyword(s):  
Potential Role ◽  
Current Status ◽  
Special Focus ◽  
Receptor Ligands ◽  
Drug Candidates ◽  
Inflammatory Conditions ◽  
Adenosine Receptor Ligands ◽  
Subtype Selective ◽  
G Protein Coupled

Background: Adenosine receptors (ARs) are classified as A1, A2A, A2B, and A3 subtypes belong to the superfamily of G-protein coupled receptors (GPCRs). More than 40% of modern medicines act through either activation or inhibition of signaling processes associated with GPCRs. In particular, A2B AR signaling pathways are implicated in asthma, inflammation, cancer, ischemic hyperfusion, diabetes mellitus, cardiovascular diseases, gastrointestinal disorders, and kidney disease. Methods: This article reviews different disease segments wherein A2B AR is implicated and discusses the potential role of subtype-selective A2B AR ligands in the management of such diseases or disorders. All the relevant publications on this topic are reviewed and presented scientifically. Results: This review provides an up-to-date highlight of the recent advances in the development of novel and selective A2B AR ligands and their therapeutic role in treating various disease conditions. A special focus has been given to the therapeutic potentials of selective A2B AR ligands in the management of airway inflammatory conditions and cancer. Conclusions: This systematic review demonstrates the current status and perspectives of A2B AR ligands as therapeutically useful agents that would assist medicinal chemists and pharmacologists in discovering novel and subtype-selective A2B AR ligands as potential drug candidates.

scholarly journals Potential role of hypovitaminosis D and vitamin D supplementation during COVID-19 pandemic

QJM ◽  
2020 ◽  
Author(s):  
M Verdoia ◽  
G De Luca
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Broad Spectrum ◽  
Potential Role ◽  
Hypovitaminosis D ◽  
Mechanisms Of Action ◽  
Vitamin D Supplementation ◽  
Current Status ◽  
Special Focus

Summary Vitamin D deficiency is a pandemic disorder affecting over 1 billion of subjects worldwide and displaying a broad spectrum of implications on cardiovascular and inflammatory disorders. Since the initial reports of the association between hypovitaminosis D and COVID-19, Vitamin D has been pointed as a potentially interesting treatment for SARS-CoV-2 infection. We provide an overview on the current status of vitamin D deficiency, the mechanisms of action of vitamin D and the current literature on the topic, with a special focus on the potential implications for COVID-19 pandemic.

Current Status in the Design and Development of Agonists and Antagonists of Adenosine A3 Receptor as Potential Therapeutic Agents

2019 ◽  
Vol 25 (25) ◽  
pp. 2772-2787 ◽  
Author(s):  
Raghu P. Mailavaram ◽  
Omar H.A. Al-Attraqchi ◽  
Supratik Kar ◽  
Shinjita Ghosh
Keyword(s):  
Drug Target ◽  
Therapeutic Agents ◽  
G Protein Coupled Receptors ◽  
Current Status ◽  
Renal Diseases ◽  
Adenosine A3 Receptor ◽  
Drug Candidates ◽  
Novel Drugs ◽  
The Family ◽  
G Protein Coupled

Adenosine receptors (ARs) belongs to the family of G-protein coupled receptors (GPCR) that are responsible for the modulation of a wide variety of physiological functions. The ARs are also implicated in many diseases such as cancer, arthritis, cardiovascular and renal diseases. The adenosine A3 receptor (A3AR) has emerged as a potential drug target for the progress of new and effective therapeutic agents for the treatment of various pathological conditions. This receptor’s involvement in many diseases and its validity as a target has been established by many studies. Both agonists and antagonists of A3AR have been extensively investigated in the last decade with the goal of developing novel drugs for treating diseases related to immune disorders, inflammation, cancer, and others. In this review, we shall focus on the medicinal chemistry of A3AR ligands, exploring the diverse chemical classes that have been projected as future leading drug candidates. Also, the recent advances in the therapeuetic applications of A3AR ligands are highlighted.

scholarly journals Exposure to emissions from Mount Etna (Sicily, Italy) and incidence of thyroid cancer: a geographic analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Paolo Boffetta ◽  
Lorenzo Memeo ◽  
Dario Giuffrida ◽  
Margherita Ferrante ◽  
Salvatore Sciacca
Keyword(s):  
Regression Analysis ◽  
Thyroid Cancer ◽  
Potential Role ◽  
Incidence Rates ◽  
Mount Etna ◽  
Sensitivity Analyses ◽  
Molecular Characteristics ◽  
Special Focus ◽  
Northeastern Sicily

AbstractAn increased incidence of thyroid cancer has been reported in the area close to Mount Etna, the largest volcano in Europe located in Northeastern Sicily. We tested the hypothesis that exposure to the emissions from the volcano is associated with thyroid cancer in 186 municipalities from three provinces surrounding the volcano (1.9 million inhabitants). We measured the angle between the bearing of the municipalities and each direction, with special focus on South-East, the prevalent direction of the plume, and conducted a regression analysis on 2003–2016 incidence rates of thyroid cancer, adjusting for distance from Mount Etna, population size, and income. A 10-degree increase in the angle with South-East was associated with a decrease in thyroid cancer rates in the whole population (− 0.67 cases/100,000, p = 0.002) and in women (− 1.54/100,000, p < 0.001), and were robust to several sensitivity analyses. Similar results were obtained for East-South-East direction. These results support the hypothesis of a potential role of exposure to the plume from Mount Etna in determining the high rates of thyroid cancer. The results need to be confirmed in analytical studies, in which information of exposure to chemicals originating from the volcano, as well as other possible causes, should be carefully measured, molecular characteristics of the tumors and taken into account.

scholarly journals Current status and potential role of circular RNAs in neurological disorders

2019 ◽  
Vol 150 (3) ◽  
pp. 237-248 ◽  
Author(s):  
Shanshan Lu ◽  
Xue Yang ◽  
Chudong Wang ◽  
Siqi Chen ◽  
Shuang Lu ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Potential Role ◽  
Current Status ◽  
Circular Rnas

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

scholarly journals The Contribution of Formyl Peptide Receptor Dysfunction to the Course of Neuroinflammation: A Potential Role in the Brain Pathology

2020 ◽  
Vol 18 (3) ◽  
pp. 229-249 ◽  
Author(s):  
Ewa Trojan ◽  
Natalia Bryniarska ◽  
Monika Leśkiewicz ◽  
Magdalena Regulska ◽  
Katarzyna Chamera ◽  
...  
Keyword(s):  
Potential Role ◽  
Membrane Receptors ◽  
Formyl Peptide Receptor ◽  
Proinflammatory Response ◽  
Formyl Peptide ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
The Brain

: Chronic inflammatory processes within the central nervous system (CNS) are in part responsible for the development of neurodegenerative and psychiatric diseases. These processes are associated with, among other things, the increased and disturbed activation of microglia and the elevated production of proinflammatory factors. Recent studies indicated that the disruption of the process of resolution of inflammation (RoI) may be the cause of CNS disorders. It is shown that the RoI is regulated by endogenous molecules called specialized pro-resolving mediators (SPMs), which interact with specific membrane receptors. Some SPMs activate formyl peptide receptors (FPRs), which belong to the family of seven-transmembrane G protein-coupled receptors. These receptors take part not only in the proinflammatory response but also in the resolution of the inflammation process. Therefore, the activation of FPRs might have complex consequences. : This review discusses the potential role of FPRs, and in particular the role of FPR2 subtype, in the brain under physiological and pathological conditions and their involvement in processes underlying neurodegenerative and psychiatric disorders as well as ischemia, the pathogenesis of which involves the dysfunction of inflammatory processes.

Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Amro M. Soliman ◽  
Srijit Das ◽  
Pasuk Mahakkanukrauh
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Vascular Aging ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Cardiovascular Pathologies ◽  
Potential Drug Targets

: There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.

scholarly journals Exploring a role for heteromerization in GPCR signalling specificity

2010 ◽  
Vol 433 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Raphael Rozenfeld ◽  
Lakshmi A. Devi
Keyword(s):  
Physiological Role ◽  
Therapeutic Effects ◽  
Receptor Ligands ◽  
Physiological Processes ◽  
Downstream Effectors ◽  
Signal Specificity ◽  
G Protein Coupled ◽  
Intracellular Milieu ◽  
Formation Of Complexes

The critical involvement of GPCRs (G-protein-coupled receptors) in nearly all physiological processes, and the presence of these receptors at the interface between the extracellular and the intracellular milieu, has positioned these receptors as pivotal therapeutic targets. Although a large number of drugs targeting GPCRs are currently available, significant efforts have been directed towards understanding receptor properties, with the goal of identifying and designing improved receptor ligands. Recent advances in GPCR pharmacology have demonstrated that different ligands binding to the same receptor can activate discrete sets of downstream effectors, a phenomenon known as ‘ligand-directed signal specificity’, which is currently being explored for drug development due to its potential therapeutic advantage. Emerging studies suggest that GPCR responses can also be modulated by contextual factors, such as interactions with other GPCRs. Association between different GPCR types leads to the formation of complexes, or GPCR heteromers, with distinct and unique signalling properties. Some of these heteromers activate discrete sets of signalling effectors upon activation by the same ligand, a phenomenon termed ‘heteromer-directed signalling specificity’. This has been shown to be involved in the physiological role of receptors and, in some cases, in disease-specific dysregulation of a receptor effect. Hence targeting GPCR heteromers constitutes an emerging strategy to select receptor-specific responses and is likely to be useful in achieving specific beneficial therapeutic effects.

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