Abstract
The adenosine pathway is a powerful evolutionarily selected mechanism aimed at a fine modulation of inflammatory responses and protection of tissues from injuries. Adenosine exerts its modulatory effects via interaction with G protein-coupled receptors, designated as A1, A2A, A2B and A3. In this regard, extracellular adenosine concentrations are critical in determining its ability of regulating several biological functions. The levels achieved by adenosine in close proximity of its receptors are strictly regulated by a variety of dynamic mechanisms, including intracellular and extracellular biosynthesis, transport and metabolism, based on tissue energy status. In this context, the catabolic enzyme adenosine deaminase (ADA) represents a critical checkpoint in the regulation of extracellular adenosine levels and, consequently, in the control of receptor stimulation, thus playing a pivotal role in the modulation of purinergic responses to several pathophysiological events, such as chronic pulmonary diseases, rheumatoid arthritis, inflammatory bowel diseases and sepsis.
This article reviews current data on the role played by ADA in the regulation of immune system activity through its modulation of adenosine pathways. Particular attention has been paid to the involvement of ADA in the pathophysiology of relevant inflammatory diseases. In addition, the interest in designing and developing novel ADA inhibitors, as new tools potentially useful for the therapeutic management of inflammatory disorders, has been discussed.
Keywords: Adenosine, adenosine deaminase, dipeptidyl-peptidase IV, immune system, inflammation, neurodegenerative diseases, immune cell cancer, adenosine deaminase inhibitors, crystallographic analysis, Ecto-Enzyme
Current Drug Targets
Title:Adenosine Deaminase in the Modulation of Immune System and its Potential as a Novel Target for Treatment of Inflammatory Disorders
Volume: 13 Issue: 6
Author(s): Luca Antonioli, Rocchina Colucci, Concettina La Motta, Marco Tuccori, Oriana Awwad, Federico Da Settimo, Corrado Blandizzi and Matteo Fornai
Affiliation:
Keywords: Adenosine, adenosine deaminase, dipeptidyl-peptidase IV, immune system, inflammation, neurodegenerative diseases, immune cell cancer, adenosine deaminase inhibitors, crystallographic analysis, Ecto-Enzyme
Abstract: The adenosine pathway is a powerful evolutionarily selected mechanism aimed at a fine modulation of inflammatory responses and protection of tissues from injuries. Adenosine exerts its modulatory effects via interaction with G protein-coupled receptors, designated as A1, A2A, A2B and A3. In this regard, extracellular adenosine concentrations are critical in determining its ability of regulating several biological functions. The levels achieved by adenosine in close proximity of its receptors are strictly regulated by a variety of dynamic mechanisms, including intracellular and extracellular biosynthesis, transport and metabolism, based on tissue energy status. In this context, the catabolic enzyme adenosine deaminase (ADA) represents a critical checkpoint in the regulation of extracellular adenosine levels and, consequently, in the control of receptor stimulation, thus playing a pivotal role in the modulation of purinergic responses to several pathophysiological events, such as chronic pulmonary diseases, rheumatoid arthritis, inflammatory bowel diseases and sepsis.
This article reviews current data on the role played by ADA in the regulation of immune system activity through its modulation of adenosine pathways. Particular attention has been paid to the involvement of ADA in the pathophysiology of relevant inflammatory diseases. In addition, the interest in designing and developing novel ADA inhibitors, as new tools potentially useful for the therapeutic management of inflammatory disorders, has been discussed.
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Cite this article as:
Antonioli Luca, Colucci Rocchina, La Motta Concettina, Tuccori Marco, Awwad Oriana, Da Settimo Federico, Blandizzi Corrado and Fornai Matteo, Adenosine Deaminase in the Modulation of Immune System and its Potential as a Novel Target for Treatment of Inflammatory Disorders, Current Drug Targets 2012; 13 (6) . https://dx.doi.org/10.2174/138945012800564095
DOI https://dx.doi.org/10.2174/138945012800564095 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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