Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy
The blood–brain barrier (BBB) is a biological barrier that protects the central nervous system (CNS) by ensuring an appropriate microenvironment. Brain microvascular endothelial cells (ECs) control the passage of molecules from blood to brain tissue and regulate their concentration-versus-time profi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/10/2441 |
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| author | Mercedes Fernandez Manuela Nigro Alessia Travagli Silvia Pasquini Fabrizio Vincenzi Katia Varani Pier Andrea Borea Stefania Merighi Stefania Gessi |
| author_facet | Mercedes Fernandez Manuela Nigro Alessia Travagli Silvia Pasquini Fabrizio Vincenzi Katia Varani Pier Andrea Borea Stefania Merighi Stefania Gessi |
| author_sort | Mercedes Fernandez |
| collection | DOAJ |
| description | The blood–brain barrier (BBB) is a biological barrier that protects the central nervous system (CNS) by ensuring an appropriate microenvironment. Brain microvascular endothelial cells (ECs) control the passage of molecules from blood to brain tissue and regulate their concentration-versus-time profiles to guarantee proper neuronal activity, angiogenesis and neurogenesis, as well as to prevent the entry of immune cells into the brain. However, the BBB also restricts the penetration of drugs, thus presenting a challenge in the development of therapeutics for CNS diseases. On the other hand, adenosine, an endogenous purine-based nucleoside that is expressed in most body tissues, regulates different body functions by acting through its G-protein-coupled receptors (A1, A2A, A2B and A3). Adenosine receptors (ARs) are thus considered potential drug targets for treating different metabolic, inflammatory and neurological diseases. In the CNS, A1 and A2A are expressed by astrocytes, oligodendrocytes, neurons, immune cells and ECs. Moreover, adenosine, by acting locally through its receptors A1 and/or A2A, may modulate BBB permeability, and this effect is potentiated when both receptors are simultaneously activated. This review showcases in vivo and in vitro evidence supporting AR signaling as a candidate for modifying endothelial barrier permeability in the treatment of CNS disorders. |
| first_indexed | 2024-03-10T20:58:25Z |
| format | Article |
| id | doaj.art-25ad692c1b684bb3a22a929700072748 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:58:25Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-25ad692c1b684bb3a22a9297000727482023-11-19T17:44:34ZengMDPI AGPharmaceutics1999-49232023-10-011510244110.3390/pharmaceutics15102441Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases TherapyMercedes Fernandez0Manuela Nigro1Alessia Travagli2Silvia Pasquini3Fabrizio Vincenzi4Katia Varani5Pier Andrea Borea6Stefania Merighi7Stefania Gessi8Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyUniversity of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyThe blood–brain barrier (BBB) is a biological barrier that protects the central nervous system (CNS) by ensuring an appropriate microenvironment. Brain microvascular endothelial cells (ECs) control the passage of molecules from blood to brain tissue and regulate their concentration-versus-time profiles to guarantee proper neuronal activity, angiogenesis and neurogenesis, as well as to prevent the entry of immune cells into the brain. However, the BBB also restricts the penetration of drugs, thus presenting a challenge in the development of therapeutics for CNS diseases. On the other hand, adenosine, an endogenous purine-based nucleoside that is expressed in most body tissues, regulates different body functions by acting through its G-protein-coupled receptors (A1, A2A, A2B and A3). Adenosine receptors (ARs) are thus considered potential drug targets for treating different metabolic, inflammatory and neurological diseases. In the CNS, A1 and A2A are expressed by astrocytes, oligodendrocytes, neurons, immune cells and ECs. Moreover, adenosine, by acting locally through its receptors A1 and/or A2A, may modulate BBB permeability, and this effect is potentiated when both receptors are simultaneously activated. This review showcases in vivo and in vitro evidence supporting AR signaling as a candidate for modifying endothelial barrier permeability in the treatment of CNS disorders.https://www.mdpi.com/1999-4923/15/10/2441blood–brain barrierbrain microvascular endothelial cellstight junction proteinsadenosine receptor signalingadenosine receptor agonistsadenosine receptor antagonist |
| spellingShingle | Mercedes Fernandez Manuela Nigro Alessia Travagli Silvia Pasquini Fabrizio Vincenzi Katia Varani Pier Andrea Borea Stefania Merighi Stefania Gessi Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy Pharmaceutics blood–brain barrier brain microvascular endothelial cells tight junction proteins adenosine receptor signaling adenosine receptor agonists adenosine receptor antagonist |
| title | Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy |
| title_full | Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy |
| title_fullStr | Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy |
| title_full_unstemmed | Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy |
| title_short | Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy |
| title_sort | strategies for drug delivery into the brain a review on adenosine receptors modulation for central nervous system diseases therapy |
| topic | blood–brain barrier brain microvascular endothelial cells tight junction proteins adenosine receptor signaling adenosine receptor agonists adenosine receptor antagonist |
| url | https://www.mdpi.com/1999-4923/15/10/2441 |
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