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REVIEW ARTICLE

Exploring the multifaceted roles of adenosine: A molecule with diverse functions

Jacqueline Fátima Martins de Almeida1 ,  Martina Contestabile1 ,  Simona Daniele1*
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1 Department of Pharmacy, Faculty of Pharmacy, University of Pisa, Pisa, Italy
GPD, 8575 https://doi.org/10.36922/gpd.8575
Submitted: 17 January 2025 | Revised: 27 February 2025 | Accepted: 28 February 2025 | Published: 27 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Adenosine is a ubiquitous molecule distributed in all eukaryotic cells of the human body. The function of adenosine varies depending on the cell type and receptor subtypes involved. For instance, adenosine 2A and 2B receptors couple with stimulatory G proteins, leading to increased intracellular cyclic adenosine 3’,5’-monophosphate (cAMP) levels upon activation. In contrast, adenosine 1 and 3 receptors couple with inhibitory G proteins, resulting in decreased intracellular cAMP levels. Consequently, an imbalance of adenosine receptor expression can affect several biological pathways and mechanisms. In the brain, where adenosine plays an important role, dysregulation of adenosine receptors has been linked to several neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, and Huntington’s disease. Adenosine also modulates cardiovascular function, influencing vasodilatation, blood pressure regulation, heart rate, and platelet activity. In addition, growing evidence highlights the impact of adenosine receptors on decision-making, habits, and goal-directed behaviors, linking them to stress-induced mood depression and other psychiatric disorders. Given the importance of adenosine modulation on human health, studying nutraceuticals and natural substances that influence adenosine could provide valuable insights. Considering the extensive physiological roles of adenosine, this review aims to summarize the diverse functions of adenosine receptors across various human tissues, emphasizing their connection to various diseases and the potential influence of external factors on their expression and functionality.

Graphical abstract
Keywords
Adenosine receptors
G protein-coupled receptors
Adenosine receptors expression
Adenosine receptors and neurological disease
Funding
We acknowledge financial support under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.1, Call for Tender No. 104, published on February 2, 2022, by the Italian Ministry of University and Research (MUR), funded by the European Union-NextGenerationEU, under the project title “Development of nano/micro-engineered devices for applications in peripheral nervous system pathological models (ENGInerve)” – CUP I53D23002260006 – Grant number: 2022ZH5M72 (449999_PRIN2022_ DANIELE_2022ZH5M72).
Conflict of interest
Simona Daniele is an editorial board member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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