Activation of Microglia by Amyloid β Requires P2X7 Receptor Expression
Open accessAbstract
Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this and other nucleotides modulates microglia responses via P2Y and P2X receptors, among which the P2X7 subtype stands out for its proinflammatory activity and for up-regulation in a transgenic model of Alzheimer disease and in brains from Alzheimer disease patients. Here we show that amyloid β (Aβ) triggered increases in intracellular Ca2+ ([Ca2+]i), ATP release, IL-1β secretion, and plasma membrane permeabilization in microglia from wild-type but not from P2X7-deleted mice. Likewise, intra-hippocampal injection of Aβ caused a large accumulation of IL-1β in wild-type but not in P2X7−/− mice. These observations suggest that Aβ activates a purinergic autocrine/paracrine stimulatory loop of which the P2X7 receptor is an obligate component. Identification of the P2X7 receptor as a non-dispensable factor of Aβ-mediated microglia stimulation may open new avenues for the treatment of Alzheimer disease.
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Aβ1-42 can activate microglia through the P2X7 pathway, probably by binding directly to the P2X7 receptor.
“It has been reported that Aβ1-42 can activate microglia through the P2X7 pathway, probably by binding directly to the P2X7 receptor.378”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [378]
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References 57 · Cited by 293
- Authors
- Sanz, J. M., Chiozzi, P., Ferrari, D., Colaianna, M., Idzko, M., Falzoni, S., Fellin, R., Trabace, L., & Di Virgilio, F.
- Affiliations
- Department of Clinical and Experimental Medicine, Section of Internal Medicine
- University of Ferrara (IT)
- University of Foggia (IT)
- University Medical Center Freiburg (DE)
- Department of Experimental and Diagnostic Medicine, Section of General Pathology
- Corresponding author
- Fellin, Renato
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-04-01
- Volume
- 182
- Issue
- 7
- Pages
- 4378-4385
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1811472601
- Cited by
- 293
- References
- 57
- Citations by year
- 2026: 16 · 2025: 9 · 2024: 23 · 2023: 11 · 2022: 23 · 2021: 18 · 2020: 21 · 2019: 19 · 2018: 21 · 2017: 21 · 2016: 13 · 2015: 14 · 2014: 23 · 2013: 14 · 2012: 18
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- P2X7 receptor, amyloid-beta, microglial activation, Alzheimer's disease, purinergic signaling, extracellular ATP, intracellular calcium, IL-1β secretion, plasma membrane permeabilization, hippocampus
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Cell Membrane Permeability, Amyloid beta-Peptides, Microglia, Receptors, Purinergic P2, Mice, Knockout, Mice, Interleukin-1beta, Receptors, Purinergic P2X7
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