The P2X7 Receptor: Central Hub of Brain Diseases
Open accessAbstract
The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the extracellular milieu. The P2X7 receptor is widely expressed in the CNS, such as frontal cortex, hippocampus, amygdala and striatum, regions involved in neurodegenerative diseases and psychiatric disorders. Despite P2X7 receptor functions in glial cells have been extensively studied, the existence and roles of this receptor in neurons are still controversially discussed. Regardless, P2X7 receptors mediate several processes observed in neuropsychiatric disorders and brain tumors, such as activation of neuroinflammatory response, stimulation of glutamate release and neuroplasticity impairment. Moreover, P2X7 receptor gene polymorphisms have been associated to depression, and isoforms of P2X7 receptors are implicated in neuropsychiatric diseases. In view of that, the P2X7 receptor has been proposed to be a potential target for therapeutic intervention in brain diseases. This review discusses the molecular mechanisms underlying P2X7 receptor-mediated signaling in neurodegenerative diseases, psychiatric disorders, and brain tumors. In addition, it highlights the recent advances in the development of P2X7 receptor antagonists that are able of penetrating the central nervous system.
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P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke.
“Remarkably, P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke [21, 92–95], as further discussed.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [95]
Inhibition of the P2X7 receptor might decrease pathological traits mediated by the RAAS pressor axis and protect against brain and lung injury in COVID-19 patients.
“Since the P2X7 receptor is also involved in lung damage [87–89], neurodegenerative and psychiatric disorders [92, 95, 118], the hypothesis is reasonable that inhibition of this receptor might decrease pathological traits mediated by the RAAS pressor axis and protect against brain and lung injury in COVID-19 patients.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [95]
The role of the P2X7 receptor in neuroinflammatory processes in neuropsychiatric and neurodegenerative diseases is widely studied.
“The role of the P2X7 receptor in neuroinflammatory processes in neuropsychiatric and neurodegenerative diseases is widely studied [95, 118].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [95]
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References 306 · Cited by 162
- Authors
- Andrejew, R., Oliveira-Giacomelli, Á., Ribeiro, D. E., Glaser, T., Arnaud-Sampaio, V. F., Lameu, C., & Ulrich, H.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Ulrich, Henning
- ORCID
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2020-07-31
- Volume
- 13
- Pages
- 124-124
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC7413029
- OpenAlex
- W3046566500
- Cited by
- 162
- References
- 306
- Citations by year
- 2026: 24 · 2025: 24 · 2024: 29 · 2023: 26 · 2022: 36 · 2021: 21 · 2020: 1
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-sa
- creativecommons.org/licenses/by/4.0/ (vor)
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2015/19128-2, 2018/07366-4, 2019/05384-8, 2019/26852-0, 2015/13345-1, 2018/17504-5)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (306392/2017-8, 141264/2017-9)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- P2X7 receptor, ATP-gated cation channels, neuroinflammation, neurodegenerative diseases, mental illness, brain tumors, neuroplasticity, glutamate release, depression, P2X7 receptor antagonists, brain drug delivery, glial cells, neurons, neuroprotection
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