Contribution of P2X4 Receptors to CNS Function and Pathophysiology
The release and extracellular action of ATP are a widespread mechanism for cell-to-cell communication in living organisms through activation of P2X and P2Y receptors expressed at the cell surface of most tissues, including the nervous system. Among ionototropic receptors, P2X4 receptors have emerged...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5562 |
| _version_ | 1797560411307900928 |
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| author | Alejandro Montilla Gilda Paloma Mata Carlos Matute Maria Domercq |
| author_facet | Alejandro Montilla Gilda Paloma Mata Carlos Matute Maria Domercq |
| author_sort | Alejandro Montilla |
| collection | DOAJ |
| description | The release and extracellular action of ATP are a widespread mechanism for cell-to-cell communication in living organisms through activation of P2X and P2Y receptors expressed at the cell surface of most tissues, including the nervous system. Among ionototropic receptors, P2X4 receptors have emerged in the last decade as a potential target for CNS disorders such as epilepsy, ischemia, chronic pain, anxiety, multiple sclerosis and neurodegenerative diseases. However, the role of P2X4 receptor in each pathology ranges from beneficial to detrimental, although the mechanisms are still mostly unknown. P2X4 is expressed at low levels in CNS cells including neurons and glial cells. In normal conditions, P2X4 activation contributes to synaptic transmission and synaptic plasticity. Importantly, one of the genes present in the transcriptional program of myeloid cell activation is P2X4. Microglial P2X4 upregulation, the P2X4<sup>+</sup> state of microglia, seems to be common in most acute and chronic neurodegenerative diseases associated with inflammation. In this review, we summarize knowledge about the role of P2X4 receptors in the CNS physiology and discuss potential pitfalls and open questions about the therapeutic potential of blocking or potentiation of P2X4 for different pathologies. |
| first_indexed | 2024-03-10T18:00:10Z |
| format | Article |
| id | doaj.art-8b9999742981478da3f25459be6471e9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:00:10Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8b9999742981478da3f25459be6471e92023-11-20T08:58:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012115556210.3390/ijms21155562Contribution of P2X4 Receptors to CNS Function and PathophysiologyAlejandro Montilla0Gilda Paloma Mata1Carlos Matute2Maria Domercq3Department of Neuroscience, University of the Basque Country (UPV/EHU), Achucarro Basque Center for Neuroscience and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, SpainDepartment of Neuroscience, University of the Basque Country (UPV/EHU), Achucarro Basque Center for Neuroscience and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, SpainDepartment of Neuroscience, University of the Basque Country (UPV/EHU), Achucarro Basque Center for Neuroscience and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, SpainDepartment of Neuroscience, University of the Basque Country (UPV/EHU), Achucarro Basque Center for Neuroscience and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, SpainThe release and extracellular action of ATP are a widespread mechanism for cell-to-cell communication in living organisms through activation of P2X and P2Y receptors expressed at the cell surface of most tissues, including the nervous system. Among ionototropic receptors, P2X4 receptors have emerged in the last decade as a potential target for CNS disorders such as epilepsy, ischemia, chronic pain, anxiety, multiple sclerosis and neurodegenerative diseases. However, the role of P2X4 receptor in each pathology ranges from beneficial to detrimental, although the mechanisms are still mostly unknown. P2X4 is expressed at low levels in CNS cells including neurons and glial cells. In normal conditions, P2X4 activation contributes to synaptic transmission and synaptic plasticity. Importantly, one of the genes present in the transcriptional program of myeloid cell activation is P2X4. Microglial P2X4 upregulation, the P2X4<sup>+</sup> state of microglia, seems to be common in most acute and chronic neurodegenerative diseases associated with inflammation. In this review, we summarize knowledge about the role of P2X4 receptors in the CNS physiology and discuss potential pitfalls and open questions about the therapeutic potential of blocking or potentiation of P2X4 for different pathologies.https://www.mdpi.com/1422-0067/21/15/5562purinergic P2X4 receptormicroglianeuroninflammationCNS disease |
| spellingShingle | Alejandro Montilla Gilda Paloma Mata Carlos Matute Maria Domercq Contribution of P2X4 Receptors to CNS Function and Pathophysiology International Journal of Molecular Sciences purinergic P2X4 receptor microglia neuron inflammation CNS disease |
| title | Contribution of P2X4 Receptors to CNS Function and Pathophysiology |
| title_full | Contribution of P2X4 Receptors to CNS Function and Pathophysiology |
| title_fullStr | Contribution of P2X4 Receptors to CNS Function and Pathophysiology |
| title_full_unstemmed | Contribution of P2X4 Receptors to CNS Function and Pathophysiology |
| title_short | Contribution of P2X4 Receptors to CNS Function and Pathophysiology |
| title_sort | contribution of p2x4 receptors to cns function and pathophysiology |
| topic | purinergic P2X4 receptor microglia neuron inflammation CNS disease |
| url | https://www.mdpi.com/1422-0067/21/15/5562 |
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