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Biomedicines
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Advances in Adenosine Receptor Research
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Advances in Adenosine Receptor Research

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (20 August 2021) | Viewed by 6772

Special Issue Editor

Dr. Natasha Irrera

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Interests: mechanism of action of drugs; tissue remodeling; nutraceuticals; pharmacovigilance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Many different intercellular signals preserve homeostasis in tissues and organs. In this context, the purinergic signaling assumes an important role. Adenosine receptors are ubiquitously expressed, engaged in the physiology and pharmacology of many tissues and organs. In the last few years, adenosine receptors have been studied as a target for many diseases including cancer, regulation of the immune system, skin fibrosis, neurodegenerative conditions, and bone metabolism disorders.

The importance of adenosine receptors signaling to human health indicates that targeting multiple steps and pathways involved in the adenosine receptor signaling, such as adenosine generation and metabolism, may be effective for the management of several diseases.

The purpose of this Special Issue is to publish original research or review articles on adenosine receptors and their possible use as therapeutic targets.

Dr. Natasha Irrera
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • purinergic signaling
  • adenosine
  • adenosine receptors
  • signaling pathways
  • therapeutic target

Published Papers (2 papers)

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Research

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21 pages, 3482 KiB  
Article
The Specificity of Downstream Signaling for A1 and A2AR Does Not Depend on the C-Terminus, Despite the Importance of This Domain in Downstream Signaling Strength
by Abhinav R. Jain, Claire McGraw and Anne S. Robinson
Biomedicines 2020, 8(12), 603; https://doi.org/10.3390/biomedicines8120603 - 13 Dec 2020
Cited by 4 | Viewed by 2314
Abstract
Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the [...] Read more.
Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the unstructured C-terminus, which has been utilized for all the adenosine receptor crystal structures obtained to date. Ligand binding for this truncated receptor has been shown to be similar to full-length receptor for A2AR. However, the C-terminus has been identified as a location for protein-protein interactions that may be critical for the physiological function of these important drug targets. We show that variants with A2AR C-terminal truncations lacked cAMP-linked signaling compared to the full-length receptor constructs transfected into mammalian cells (HEK-293). In addition, we show that in a humanized yeast system, the absence of the full-length C-terminus affected downstream signaling using a yeast MAPK response-based fluorescence assay, though full-length receptors showed native-like G-protein coupling. To further study the G protein coupling, we used this humanized yeast platform to explore coupling to human-yeast G-protein chimeras in a cellular context. Although the C-terminus was essential for Gα protein-associated signaling, chimeras of A1R with a C-terminus of A2AR coupled to the A1R-specific Gα (i.e., Gαi1 versus Gαs). This surprising result suggests that the C-terminus is important in the signaling strength, but not specificity, of the Gα protein interaction. This result has further implications in drug discovery, both in enabling the experimental use of chimeras for ligand design, and in the cautious interpretation of structure-based drug design using truncated receptors. Full article
(This article belongs to the Special Issue Advances in Adenosine Receptor Research)
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Review

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21 pages, 1435 KiB  
Review
Role of Adenosine and Purinergic Receptors in Myocardial Infarction: Focus on Different Signal Transduction Pathways
by Maria Cristina Procopio, Rita Lauro, Chiara Nasso, Scipione Carerj, Francesco Squadrito, Alessandra Bitto, Gianluca Di Bella, Antonio Micari, Natasha Irrera and Francesco Costa
Biomedicines 2021, 9(2), 204; https://doi.org/10.3390/biomedicines9020204 - 18 Feb 2021
Cited by 11 | Viewed by 3860
Abstract
Myocardial infarction (MI) is a dramatic event often caused by atherosclerotic plaque erosion or rupture and subsequent thrombotic occlusion of a coronary vessel. The low supply of oxygen and nutrients in the infarcted area may result in cardiomyocytes necrosis, replacement of intact myocardium [...] Read more.
Myocardial infarction (MI) is a dramatic event often caused by atherosclerotic plaque erosion or rupture and subsequent thrombotic occlusion of a coronary vessel. The low supply of oxygen and nutrients in the infarcted area may result in cardiomyocytes necrosis, replacement of intact myocardium with non-contractile fibrous tissue and left ventricular (LV) function impairment if blood flow is not quickly restored. In this review, we summarized the possible correlation between adenosine system, purinergic system and Wnt/β-catenin pathway and their role in the pathogenesis of cardiac damage following MI. In this context, several pathways are involved and, in particular, the adenosine receptors system shows different interactions between its members and purinergic receptors: their modulation might be effective not only for a normal functional recovery but also for the treatment of heart diseases, thus avoiding fibrosis, reducing infarcted area and limiting scaring. Similarly, it has been shown that Wnt/β catenin pathway is activated following myocardial injury and its unbalanced activation might promote cardiac fibrosis and, consequently, LV systolic function impairment. In this regard, the therapeutic benefits of Wnt inhibitors use were highlighted, thus demonstrating that Wnt/β-catenin pathway might be considered as a therapeutic target to prevent adverse LV remodeling and heart failure following MI. Full article
(This article belongs to the Special Issue Advances in Adenosine Receptor Research)
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