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Adenosine Receptors in Health and Disease
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Adenosine Receptors in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 1843

Special Issue Editor

Dr. Srdjan Vlajkovic

E-Mail Website
Guest Editor
Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Interests: sensory systems; auditory neuroscience; inner ear diseases; inner ear therapeutics; hearing loss; inflammation; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Adenosine receptors (ARs) are essential in maintaining health, while altered AR signalling contributes to various disease processes. Adenosine acts as a cytoprotective modulator in response to stress and tissue injury, and understanding AR function is crucial for developing targeted therapies for multiple diseases.

AR signalling regulates physiological functions in the nervous, cardiovascular, and immune systems. For example, ARs regulate blood flow by inducing vasodilation, aiding tissue oxygenation, and protecting against ischemic injuries.

Dysregulation of AR signalling can lead to various pathological conditions, such as pain, cancer, neurodegenerative, inflammatory, and autoimmune diseases. In inflammatory conditions, AR modulation can either suppress or exacerbate immune responses. AR malfunction is also associated with neurological disorders such as epilepsy and Parkinson’s disease.

We invite investigators to contribute original research articles and review articles addressing the various roles of AR in physiology and pathophysiology. Please note that pure clinical or model studies are unsuitable for this journal, but clinical submissions with biomolecular studies are welcome.

Dr. Srdjan Vlajkovic
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • adenosine
  • adenosine receptors
  • P1 receptors
  • A1 receptor
  • A2A receptor
  • A2B receptor
  • A3 receptor
  • adenosine deaminase
  • adenosine kinase
  • adenosine transporters
  • adenosine receptor agonists
  • adenosine receptor antagonists
  • caffeine

Published Papers (5 papers)

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Research

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19 pages, 1470 KiB  
Article
Adenosine A2A Receptor Blockade Provides More Effective Benefits at the Onset Rather than after Overt Neurodegeneration in a Rat Model of Parkinson’s Disease
by Ana Carla L. Nunes, Marta Carmo, Andrea Behrenswerth, Paula M. Canas, Paula Agostinho and Rodrigo A. Cunha
Int. J. Mol. Sci. 2024, 25(9), 4903; https://doi.org/10.3390/ijms25094903 - 30 Apr 2024
Viewed by 384
Abstract
Adenosine A2A receptor (A2AR) antagonists are the leading nondopaminergic therapy to manage Parkinson’s disease (PD) since they afford both motor benefits and neuroprotection. PD begins with a synaptic dysfunction and damage in the striatum evolving to an overt neuronal damage [...] Read more.
Adenosine A2A receptor (A2AR) antagonists are the leading nondopaminergic therapy to manage Parkinson’s disease (PD) since they afford both motor benefits and neuroprotection. PD begins with a synaptic dysfunction and damage in the striatum evolving to an overt neuronal damage of dopaminergic neurons in the substantia nigra. We tested if A2AR antagonists are equally effective in controlling these two degenerative processes. We used a slow intracerebroventricular infusion of the toxin MPP+ in male rats for 15 days, which caused an initial loss of synaptic markers in the striatum within 10 days, followed by a neuronal loss in the substantia nigra within 30 days. Interestingly, the initial loss of striatal nerve terminals involved a loss of both dopaminergic and glutamatergic synaptic markers, while GABAergic markers were preserved. The daily administration of the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) in the first 10 days after MPP+ infusion markedly attenuated both the initial loss of striatal synaptic markers and the subsequent loss of nigra dopaminergic neurons. Strikingly, the administration of SCH58261 (0.1 mg/kg, i.p. for 10 days) starting 20 days after MPP+ infusion was less efficacious to attenuate the loss of nigra dopaminergic neurons. This prominent A2AR-mediated control of synaptotoxicity was directly confirmed by showing that the MPTP-induced dysfunction (MTT assay) and damage (lactate dehydrogenase release assay) of striatal synaptosomes were prevented by 50 nM SCH58261. This suggests that A2AR antagonists may be more effective to counteract the onset rather than the evolution of PD pathology. Full article
(This article belongs to the Special Issue Adenosine Receptors in Health and Disease)
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Review

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23 pages, 3058 KiB  
Review
Translational Experimental Basis of Indirect Adenosine Receptor Agonist Stimulation for Bone Regeneration: A Review
by Quinn T. Ehlen, Nicholas A. Mirsky, Blaire V. Slavin, Marcelo Parra, Vasudev Vivekanand Nayak, Bruce Cronstein, Lukasz Witek and Paulo G. Coelho
Int. J. Mol. Sci. 2024, 25(11), 6104; https://doi.org/10.3390/ijms25116104 (registering DOI) - 1 Jun 2024
Abstract
Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature [...] Read more.
Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature review of the PubMed database with relevant keywords was conducted. The search criteria involved in vitro or in vivo models, with clear methodological descriptions. Only studies that included the use of indirect adenosine agonists, looking at the effects of bone regeneration, were considered relevant according to the eligibility criteria. A total of 29 articles were identified which met the inclusion and exclusion criteria, and they were reviewed to highlight the preclinical translation of adenosine agonists. While preclinical studies demonstrate the therapeutic potential of adenosine signaling in bone regeneration, its clinical application remains unrealized, underscoring the need for further clinical trials. To date, only large, preclinical animal models using indirect adenosine agonists have been successful in stimulating bone regeneration. The adenosine receptors (A1, A2A, A2B, and A3) stimulate various pathways, inducing different cellular responses. Specifically, indirect adenosine agonists act to increase the extracellular concentration of adenosine, subsequently agonizing the respective adenosine receptors. The agonism of each receptor is dependent on its expression on the cell surface, the extracellular concentration of adenosine, and its affinity for adenosine. This comprehensive review analyzed the multitude of indirect agonists currently being studied preclinically for bone regeneration, discussing the mechanisms of each agonist, their cellular responses in vitro, and their effects on bone formation in vivo. Full article
(This article belongs to the Special Issue Adenosine Receptors in Health and Disease)
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13 pages, 709 KiB  
Review
Adenosine in Interventional Cardiology: Physiopathologic and Pharmacologic Effects in Coronary Artery Disease
by Enrico Marchi, Iacopo Muraca, Martina Berteotti, Anna Maria Gori, Renato Valenti and Rossella Marcucci
Int. J. Mol. Sci. 2024, 25(11), 5852; https://doi.org/10.3390/ijms25115852 - 28 May 2024
Viewed by 209
Abstract
This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure [...] Read more.
This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine’s rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine’s involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine’s mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches. Full article
(This article belongs to the Special Issue Adenosine Receptors in Health and Disease)
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22 pages, 1680 KiB  
Review
Adenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases
by Luxia Chen, Xuan Lei and Karsten Mahnke
Int. J. Mol. Sci. 2024, 25(11), 5810; https://doi.org/10.3390/ijms25115810 - 27 May 2024
Viewed by 232
Abstract
Inflammatory skin diseases highlight inflammation as a central driver of skin pathologies, involving a multiplicity of mediators and cell types, including immune and non-immune cells. Adenosine, a ubiquitous endogenous immune modulator, generated from adenosine triphosphate (ATP), acts via four G protein-coupled receptors (A [...] Read more.
Inflammatory skin diseases highlight inflammation as a central driver of skin pathologies, involving a multiplicity of mediators and cell types, including immune and non-immune cells. Adenosine, a ubiquitous endogenous immune modulator, generated from adenosine triphosphate (ATP), acts via four G protein-coupled receptors (A1, A2A, A2B, and A3). Given the widespread expression of those receptors and their regulatory effects on multiple immune signaling pathways, targeting adenosine receptors emerges as a compelling strategy for anti-inflammatory intervention. Animal models of psoriasis, contact hypersensitivity (CHS), and other dermatitis have elucidated the involvement of adenosine receptors in the pathogenesis of these conditions. Targeting adenosine receptors is effective in attenuating inflammation and remodeling the epidermal structure, potentially showing synergistic effects with fewer adverse effects when combined with conventional therapies. What is noteworthy are the promising outcomes observed with A2A agonists in animal models and ongoing clinical trials investigating A3 agonists, underscoring a potential therapeutic approach for the management of inflammatory skin disorders. Full article
(This article belongs to the Special Issue Adenosine Receptors in Health and Disease)
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18 pages, 1408 KiB  
Review
Adenosine A3 Receptor: From Molecular Signaling to Therapeutic Strategies for Heart Diseases
by Ratchanee Duangrat, Warisara Parichatikanond, Wisinee Chanmahasathien and Supachoke Mangmool
Int. J. Mol. Sci. 2024, 25(11), 5763; https://doi.org/10.3390/ijms25115763 - 25 May 2024
Viewed by 428
Abstract
Cardiovascular diseases (CVDs), particularly heart failure, are major contributors to early mortality globally. Heart failure poses a significant public health problem, with persistently poor long-term outcomes and an overall unsatisfactory prognosis for patients. Conventionally, treatments for heart failure have focused on lowering blood [...] Read more.
Cardiovascular diseases (CVDs), particularly heart failure, are major contributors to early mortality globally. Heart failure poses a significant public health problem, with persistently poor long-term outcomes and an overall unsatisfactory prognosis for patients. Conventionally, treatments for heart failure have focused on lowering blood pressure; however, the development of more potent therapies targeting hemodynamic parameters presents challenges, including tolerability and safety risks, which could potentially restrict their clinical effectiveness. Adenosine has emerged as a key mediator in CVDs, acting as a retaliatory metabolite produced during cellular stress via ATP metabolism, and works as a signaling molecule regulating various physiological processes. Adenosine functions by interacting with different adenosine receptor (AR) subtypes expressed in cardiac cells , including A1AR, A2AAR, A2BAR, and A3AR. In addition to A1AR, A3AR has a multifaceted role in the cardiovascular system, since its activation contributes to reducing the damage to the heart in various pathological states, particularly ischemic heart disease, heart failure, and hypertension, although its role is not as well documented compared to other AR subtypes. Research on A3AR signaling has focused on identifying the intricate molecular mechanisms involved in CVDs through various pathways, including Gi or Gq protein-dependent signaling, ATP-sensitive potassium channels, MAPKs, and G protein-independent signaling. Several A3AR-specific agonists, such as piclidenoson and namodenoson, exert cardioprotective impacts during ischemia in the diverse animal models of heart disease. Thus, modulating A3ARs serves as a potential therapeutic approach, fueling considerable interest in developing compounds that target A3ARs as potential treatments for heart diseases. Full article
(This article belongs to the Special Issue Adenosine Receptors in Health and Disease)
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