ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases
Ectonucleoside triphosphate diphosphohydrolases (ENTPDases), members of the cluster of differentiation 39 (CD39) family, are key regulators of purinergic signaling through the hydrolysis of tri and diphosphate nucleotides. These enzymes are expressed on the cell surface, extracellular environment, o...
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Open Exploration Publishing Inc.
2025-05-01
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| Series: | Exploration of Neuroscience |
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| Online Access: | https://www.explorationpub.com/uploads/Article/A100691/100691.pdf |
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| author | Isadora Cunha Ribeiro Amanda Laviola de Andrade Vitória de Almeida Rodrigues Markson Suarez Lacôrte Lima Juliana Lopes Rangel Fietto |
| author_facet | Isadora Cunha Ribeiro Amanda Laviola de Andrade Vitória de Almeida Rodrigues Markson Suarez Lacôrte Lima Juliana Lopes Rangel Fietto |
| author_sort | Isadora Cunha Ribeiro |
| collection | DOAJ |
| description | Ectonucleoside triphosphate diphosphohydrolases (ENTPDases), members of the cluster of differentiation 39 (CD39) family, are key regulators of purinergic signaling through the hydrolysis of tri and diphosphate nucleotides. These enzymes are expressed on the cell surface, extracellular environment, or within intracellular organelles such as the Golgi apparatus. ENTPDases play critical roles in modulating immune responses, inflammation, and neuroinflammation by controlling extracellular nucleotide availability in mammals. Moreover, they contribute to adenosine-mediated signaling in cooperation with 5’-nucleotidases (CD73). Pathogenic microorganisms also express ENTPDases, manipulating host purinergic signaling, suppressing adenosine triphosphate (ATP)-driven inflammation, and promoting immune evasion via increased adenosine production. Pathogenic parasites also express ENTPDases, manipulating host purinergic signaling, suppressing ATP-driven inflammation, and promoting immune evasion via increased adenosine production. Given their involvement in infection and inflammatory diseases, ENTPDases have emerged as promising pharmacological targets. This review comprehensively analyzes the ENTPDases from mammals and pathogenic parasites, emphasizing their role in purinergic signaling and their potential as therapeutic targets. While ENTPDase inhibitors hold promise for modulating inflammation and infection, their clinical translation faces challenges, including selectivity, off-target effects, and systemic alterations in purinergic homeostasis. Addressing these concerns through targeted drug delivery, allosteric modulation, and improved inhibitor specificity is crucial for therapeutic advancements. |
| format | Article |
| id | doaj-art-b6fd738bbd604c19b3ef59591b0d5dcc |
| institution | DOAJ |
| issn | 2834-5347 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Neuroscience |
| spelling | doaj-art-b6fd738bbd604c19b3ef59591b0d5dcc2025-08-20T03:05:56ZengOpen Exploration Publishing Inc.Exploration of Neuroscience2834-53472025-05-01410069110.37349/en.2025.100691ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseasesIsadora Cunha Ribeiro0https://orcid.org/0000-0003-1695-8080Amanda Laviola de Andrade1https://orcid.org/0009-0004-6555-9144Vitória de Almeida Rodrigues2https://orcid.org/0009-0002-0262-2631Markson Suarez Lacôrte Lima3https://orcid.org/0009-0005-1415-0493Juliana Lopes Rangel Fietto4https://orcid.org/0000-0001-6122-1710Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa 36570-900, MG, BrazilDepartamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa 36570-900, MG, BrazilDepartamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa 36570-900, MG, BrazilDepartamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa 36570-900, MG, BrazilDepartamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa 36570-900, MG, BrazilEctonucleoside triphosphate diphosphohydrolases (ENTPDases), members of the cluster of differentiation 39 (CD39) family, are key regulators of purinergic signaling through the hydrolysis of tri and diphosphate nucleotides. These enzymes are expressed on the cell surface, extracellular environment, or within intracellular organelles such as the Golgi apparatus. ENTPDases play critical roles in modulating immune responses, inflammation, and neuroinflammation by controlling extracellular nucleotide availability in mammals. Moreover, they contribute to adenosine-mediated signaling in cooperation with 5’-nucleotidases (CD73). Pathogenic microorganisms also express ENTPDases, manipulating host purinergic signaling, suppressing adenosine triphosphate (ATP)-driven inflammation, and promoting immune evasion via increased adenosine production. Pathogenic parasites also express ENTPDases, manipulating host purinergic signaling, suppressing ATP-driven inflammation, and promoting immune evasion via increased adenosine production. Given their involvement in infection and inflammatory diseases, ENTPDases have emerged as promising pharmacological targets. This review comprehensively analyzes the ENTPDases from mammals and pathogenic parasites, emphasizing their role in purinergic signaling and their potential as therapeutic targets. While ENTPDase inhibitors hold promise for modulating inflammation and infection, their clinical translation faces challenges, including selectivity, off-target effects, and systemic alterations in purinergic homeostasis. Addressing these concerns through targeted drug delivery, allosteric modulation, and improved inhibitor specificity is crucial for therapeutic advancements.https://www.explorationpub.com/uploads/Article/A100691/100691.pdfentpdaseinhibitorspurinergic signalinginfectioninflammationneuroinflammationimmune modulation |
| spellingShingle | Isadora Cunha Ribeiro Amanda Laviola de Andrade Vitória de Almeida Rodrigues Markson Suarez Lacôrte Lima Juliana Lopes Rangel Fietto ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases Exploration of Neuroscience entpdase inhibitors purinergic signaling infection inflammation neuroinflammation immune modulation |
| title | ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases |
| title_full | ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases |
| title_fullStr | ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases |
| title_full_unstemmed | ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases |
| title_short | ENTPDase inhibitors: therapeutic potential in infectious, inflammatory, and neuroinflammatory diseases |
| title_sort | entpdase inhibitors therapeutic potential in infectious inflammatory and neuroinflammatory diseases |
| topic | entpdase inhibitors purinergic signaling infection inflammation neuroinflammation immune modulation |
| url | https://www.explorationpub.com/uploads/Article/A100691/100691.pdf |
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