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Block of purinergic P2X(7) receptor is neuroprotective in an animal model of Alzheimer's disease


Year of Publication:
Contact PI Name:
James G. McLarnon
Contact PI Affiliation:
Department of Anesthesiology, Pharmacology and Therapeutics,The University of British Columbia,Vancouver, British Columbia, Canada
Jae K. Ryu
Primary Reference (PubMED ID):
Funding Source:
Pacific Alzheimer Research Foundation
Michael Smith Memorial Fellowship
Study Goal and Principal Findings:

Pharmacological antagonism of the ionotropic purinergic receptor- P2X7R has been studied for effects on inflammatory reactivity and neuronal viability in amyloid-beta1-42-injected rat hippocampus. Amyloid-beta1-42-injected brains (7-day postinjection) demonstrated marked increases in P2X7R expression, gliosis, leakiness of blood-brain barrier and loss of hippocampal neurons. The P2X7R antagonist, Brilliant Blue G reduced levels of purinergic receptor expression, attenuated gliosis, diminished leakiness of blood-brain barrier and was neuroprotective in peptide-injected brain. Brilliant Blue G also demonstrated neuroprotection and antagonism against inflammatory responses induced by the P2X7R agonist, 2',3'-(benzoyl-4-benzoyl)-ATP. This study has shown intrahippocampal injection of Ab1–42  or the P2X7R ligand BzATP is associated with increased inflammatory reactivity, BBB leakiness and neurodegeneration.  Antagonism of P2X7R is suggested as a novel maneuver to reduce the consequences of inflammatory reactivity in AD brain.The findings constitute the first report that pharmacological inhibition of P2X7R, possibly by acting to inhibit inflammatory reactivity, confers neuroprotection in an animal model of Alzheimer's disease brain.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Brilliant Blue G (BBG)
Therapeutic Target:
P2X7 Purinergic Receptor
Therapy Type:
Small Molecule
Therapeutic Agent:
BzATP [20;30-(benzoyl-4-benzoyl-ATP)]
Therapeutic Target:
P2X7 Purinergic Receptor

Animal Model

Model Information:
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
Not Applicable

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Purinergic P2X7 Receptor
Activated Astrocytes
Activated Microglia
Blood Brain Barrier Integrity
Cell Biology
Neuroprotection-Amyloid Neurotoxicity