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Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation
Alzheimer’s, Parkinson’s, and multiple sclerosis are neurodegenerative diseases related by neuronal degeneration and death in specific areas of the central nervous system. These pathologies are associated with neuroinflammation, which is involved in disease progression, and halting this process repr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926490/ https://www.ncbi.nlm.nih.gov/pubmed/33672225 http://dx.doi.org/10.3390/molecules26041188 |
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author | Marucci, Gabriella Ben, Diego Dal Lambertucci, Catia Navia, Aleix Martí Spinaci, Andrea Volpini, Rosaria Buccioni, Michela |
author_facet | Marucci, Gabriella Ben, Diego Dal Lambertucci, Catia Navia, Aleix Martí Spinaci, Andrea Volpini, Rosaria Buccioni, Michela |
author_sort | Marucci, Gabriella |
collection | PubMed |
description | Alzheimer’s, Parkinson’s, and multiple sclerosis are neurodegenerative diseases related by neuronal degeneration and death in specific areas of the central nervous system. These pathologies are associated with neuroinflammation, which is involved in disease progression, and halting this process represents a potential therapeutic strategy. Evidence suggests that microglia function is regulated by A(1) and A(2A) adenosine receptors (AR), which are considered as neuroprotective and neurodegenerative receptors, respectively. The manuscript’s aim is to elucidate the role of these receptors in neuroinflammation modulation through potent and selective A(1)AR agonists (N(6)-cyclopentyl-2′- or 3′-deoxyadenosine substituted or unsubstituted in 2 position) and A(2A)AR antagonists (9-ethyl-adenine substituted in 8 and/or in 2 position), synthesized in house, using N13 microglial cells. In addition, the combined therapy of A(1)AR agonists and A(2A)AR antagonists to modulate neuroinflammation was evaluated. Results showed that A(1)AR agonists were able, to varying degrees, to prevent the inflammatory effect induced by cytokine cocktail (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ), while A(2A)AR antagonists showed a good ability to counteract neuroinflammation. Moreover, the effect achieved by combining the two most effective compounds (1 and 6) in doses previously found to be non-effective was greater than the treatment effect of each of the two compounds used separately at maximal dose. |
format | Online Article Text |
id | pubmed-7926490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79264902021-03-04 Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation Marucci, Gabriella Ben, Diego Dal Lambertucci, Catia Navia, Aleix Martí Spinaci, Andrea Volpini, Rosaria Buccioni, Michela Molecules Article Alzheimer’s, Parkinson’s, and multiple sclerosis are neurodegenerative diseases related by neuronal degeneration and death in specific areas of the central nervous system. These pathologies are associated with neuroinflammation, which is involved in disease progression, and halting this process represents a potential therapeutic strategy. Evidence suggests that microglia function is regulated by A(1) and A(2A) adenosine receptors (AR), which are considered as neuroprotective and neurodegenerative receptors, respectively. The manuscript’s aim is to elucidate the role of these receptors in neuroinflammation modulation through potent and selective A(1)AR agonists (N(6)-cyclopentyl-2′- or 3′-deoxyadenosine substituted or unsubstituted in 2 position) and A(2A)AR antagonists (9-ethyl-adenine substituted in 8 and/or in 2 position), synthesized in house, using N13 microglial cells. In addition, the combined therapy of A(1)AR agonists and A(2A)AR antagonists to modulate neuroinflammation was evaluated. Results showed that A(1)AR agonists were able, to varying degrees, to prevent the inflammatory effect induced by cytokine cocktail (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ), while A(2A)AR antagonists showed a good ability to counteract neuroinflammation. Moreover, the effect achieved by combining the two most effective compounds (1 and 6) in doses previously found to be non-effective was greater than the treatment effect of each of the two compounds used separately at maximal dose. MDPI 2021-02-23 /pmc/articles/PMC7926490/ /pubmed/33672225 http://dx.doi.org/10.3390/molecules26041188 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Marucci, Gabriella Ben, Diego Dal Lambertucci, Catia Navia, Aleix Martí Spinaci, Andrea Volpini, Rosaria Buccioni, Michela Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation |
title | Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation |
title_full | Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation |
title_fullStr | Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation |
title_full_unstemmed | Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation |
title_short | Combined Therapy of A(1)AR Agonists and A(2A)AR Antagonists in Neuroinflammation |
title_sort | combined therapy of a(1)ar agonists and a(2a)ar antagonists in neuroinflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926490/ https://www.ncbi.nlm.nih.gov/pubmed/33672225 http://dx.doi.org/10.3390/molecules26041188 |
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