P2X7 Receptor Protein

P2X7 Receptor Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">P2X7 Receptor Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>P2X7 Receptor</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[P2RX7](/proteins/p2rx7-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q99572](https://www.uniprot.org/uniprot/Q99572)</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>5U1L, 6U9V, 7KB5</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>66 kDa (monomer)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, lipid rafts</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>P2X purinergic receptor family</td>
</tr>
<tr>
<td class="label">Drug/Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Brilacidin</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">AZD9056</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">CE-224535</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">JNJ-47965567</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">Brilliant Blue G</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">A-438079</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">

P2X7 Receptor Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">P2X7 Receptor Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>P2X7 Receptor</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[P2RX7](/proteins/p2rx7-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q99572](https://www.uniprot.org/uniprot/Q99572)</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>5U1L, 6U9V, 7KB5</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>66 kDa (monomer)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, lipid rafts</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>P2X purinergic receptor family</td>
</tr>
<tr>
<td class="label">Drug/Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Brilacidin</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">AZD9056</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">CE-224535</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">JNJ-47965567</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">Brilliant Blue G</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">A-438079</td>
<td>P2X7 antagonist</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">89 edges</a></td>
</tr>
</table>

P2X7 Receptor Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

The P2X7 receptor is an ATP-gated ion channel that plays a critical role in immune signaling and neuroinflammation. It is unique among P2X receptors for its ability to form large pores that allow passage of molecules up to 900 Da when repeatedly activated. This makes it a key player in the innate immune response and a therapeutic target for neurodegenerative diseases. [@sperlgh2017]

Overview

P2X7 is a purinergic receptor that responds to extracellular ATP and mediates fast calcium influx and inflammatory signaling. P2X7 activation triggers NLRP3 inflammasome assembly, cytokine release, and cell death. It is expressed in [microglia](/cell-types/microglia-neuroinflammation) and immune cells and is a therapeutic target for neuroinflammatory diseases. [@mirasportugal2021]

This protein is involved in: [@liu2020]

• ATP signaling: Responds to extracellular ATP
• Inflammasome activation: Triggers NLRP3 and IL-1β release
• Cell death: Mediates [apoptosis](/entities/apoptosis) and [necroptosis](/entities/necroptosis)
• Disease associations: Alzheimer's disease, Parkinson's disease, depression, chronic pain

Protein Overview

Structure

The P2X7 receptor is a trimeric ATP-gated ion channel with the following structural features:

• Two Transmembrane Domains: TM1 and TM2 helices that form the ion pore
• Extracellular Loop: Contains the ATP-binding site and is heavily glycosylated
• Intracellular N- and C-termini: The C-terminus is notably long (~200 aa) and contains interaction domains
• C-terminal Protein-Protein Interaction Domain: Mediates formation of the large pore complex

Normal Function

P2X7 receptors mediate rapid ATP signaling in immune cells:

In the central nervous system, P2X7 is expressed on microglia, [astrocytes](/entities/astrocytes), [neurons](/entities/neurons), and oligodendrocyte progenitor cells.

Role in Disease

Alzheimer's Disease

P2X7 contributes to AD pathogenesis through:

• Microglial Activation: Chronic ATP release from amyloid plaques activates P2X7 on microglia
• [NLRP3 Inflammasome](/entities/nlrp3-inflammasome): P2X7-mediated inflammasome activation increases IL-1β and IL-18
• Amyloid Processing: Influences [APP](/entities/app-protein) processing and [Aβ](/proteins/amyloid-beta) clearance
• Synaptic Dysfunction: Affects synaptic plasticity and neuronal survival

Parkinson's Disease

In PD, P2X7:

• Mediates neuroinflammation in the substantia nigra
• Contributes to dopaminergic neuron death
• May interact with [α-synuclein](/proteins/alpha-synuclein) aggregation pathways
• Influences microglial phagocytosis of debris

Amyotrophic Lateral Sclerosis

P2X7 in ALS:

• Upregulated in microglia and astrocytes in SOD1 and [C9orf72](/entities/c9orf72) models
• Contributes to neuroinflammation and motor neuron vulnerability
• P2X7 antagonists show protective effects in preclinical models

Multiple Sclerosis

P2X7 signaling:

• Promotes demyelination through oligodendrocyte death
• Modulates T-cell responses
• Being targeted by BTK inhibitors in clinical trials

Molecular Mechanisms

Signaling Cascades

P2X7 activates multiple downstream pathways:

• NLRP3 Inflammasome: Pannexin-1 pore → K+ efflux → ASC speck formation → caspase-1 activation
• MAPK Pathways: ERK1/2, JNK, and p38 activation in immune cells
• [NF-κB](/entities/nf-kb) Pathway: Pro-inflammatory gene transcription
• PI3K/Akt Pathway: Cell survival signaling
• Calcium Signaling: Ca2+-dependent protease and phosphatase activation

Protein Interactions

Key interacting proteins include:

• Pannexin-1 (large pore formation)
• NLRP3 and ASC (inflammasome)
• Src family kinases (phosphorylation)
• β-catenin (transcription regulation)

Therapeutic Targeting

P2X7 is a major drug target for neuroinflammation:

BTK inhibitors (tolebrutinib, fenestrinib) indirectly modulate P2X7 signaling.

Research Directions

Current areas of investigation:

Key Publications

Background

The study of P2X7 Receptor Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• P2RX7 Gene
• [Proteins Index](/proteins)
• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• ATP Signaling
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome) [Microglia](/cell-types/microglia)

External Links

• [UniProt - P2X7 Receptor](https://www.uniprot.org/uniprot/Q99572)
• [PDB - P2X7 Structures](https://www.rcsb.org/)
• [AlphaFold - P2RX7](https://alphafold.ebi.ac.uk/entry/Q99572)
• [IUPHAR - P2X7 Receptor](https://www.guidetopharmacology.org/target/3066)

References