Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor
Epilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2380 |
| _version_ | 1797479249143136256 |
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| author | Beatriz Gil Jonathon Smith Yong Tang Peter Illes Tobias Engel |
| author_facet | Beatriz Gil Jonathon Smith Yong Tang Peter Illes Tobias Engel |
| author_sort | Beatriz Gil |
| collection | DOAJ |
| description | Epilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple comorbidities, thereby further reducing the quality of life of patients. Increasing evidence suggests purinergic signalling via extracellularly released ATP as shared pathological mechanisms across numerous brain diseases. Once released, ATP activates specific purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Among brain diseases, the P2X7R has attracted particular attention as a therapeutic target. The P2X7R is an important driver of inflammation, and its activation requires high levels of extracellular ATP to be reached under pathological conditions. Suggesting the therapeutic potential of drugs targeting the P2X7R for epilepsy, P2X7R expression increases following status epilepticus and during epilepsy, and P2X7R antagonism modulates seizure severity and epilepsy development. P2X7R antagonism has, however, also been shown to be effective in treating conditions most commonly associated with epilepsy such as psychiatric disorders and cognitive deficits, which suggests that P2X7R antagonisms may provide benefits beyond seizure control. This review summarizes the evidence suggesting drugs targeting the P2X7R as a novel treatment strategy for epilepsy with a particular focus of its potential impact on epilepsy-associated comorbidities. |
| first_indexed | 2024-03-09T21:43:07Z |
| format | Article |
| id | doaj.art-77750c61323a4a3fa6f7c8a3ef7d257d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:07Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-77750c61323a4a3fa6f7c8a3ef7d257d2023-11-23T20:24:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234238010.3390/ijms23042380Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 ReceptorBeatriz Gil0Jonathon Smith1Yong Tang2Peter Illes3Tobias Engel4Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandInternational Collaborative Centre on Big Science Plan for Purinergic Signaling, Chengdu University of TCM, Chengdu 610075, ChinaInternational Collaborative Centre on Big Science Plan for Purinergic Signaling, Chengdu University of TCM, Chengdu 610075, ChinaDepartment of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandEpilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple comorbidities, thereby further reducing the quality of life of patients. Increasing evidence suggests purinergic signalling via extracellularly released ATP as shared pathological mechanisms across numerous brain diseases. Once released, ATP activates specific purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Among brain diseases, the P2X7R has attracted particular attention as a therapeutic target. The P2X7R is an important driver of inflammation, and its activation requires high levels of extracellular ATP to be reached under pathological conditions. Suggesting the therapeutic potential of drugs targeting the P2X7R for epilepsy, P2X7R expression increases following status epilepticus and during epilepsy, and P2X7R antagonism modulates seizure severity and epilepsy development. P2X7R antagonism has, however, also been shown to be effective in treating conditions most commonly associated with epilepsy such as psychiatric disorders and cognitive deficits, which suggests that P2X7R antagonisms may provide benefits beyond seizure control. This review summarizes the evidence suggesting drugs targeting the P2X7R as a novel treatment strategy for epilepsy with a particular focus of its potential impact on epilepsy-associated comorbidities.https://www.mdpi.com/1422-0067/23/4/2380epilepsycomorbiditiespurinergic signallingATPP2X7 receptor |
| spellingShingle | Beatriz Gil Jonathon Smith Yong Tang Peter Illes Tobias Engel Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor International Journal of Molecular Sciences epilepsy comorbidities purinergic signalling ATP P2X7 receptor |
| title | Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor |
| title_full | Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor |
| title_fullStr | Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor |
| title_full_unstemmed | Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor |
| title_short | Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor |
| title_sort | beyond seizure control treating comorbidities in epilepsy via targeting of the p2x7 receptor |
| topic | epilepsy comorbidities purinergic signalling ATP P2X7 receptor |
| url | https://www.mdpi.com/1422-0067/23/4/2380 |
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