P2X7 Mediates Superoxide Production in Primary Microglia and Is Up-regulated in a Transgenic Mouse Model of Alzheimer's Disease
Open accessAbstract
Primary rat microglia stimulated with either ATP or 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) release copious amounts of superoxide (O(2)(-)*). ATP and BzATP stimulate O(2)(-)* production through purinergic receptors, primarily the P2X(7) receptor. O(2)(-)* is produced through the activation of the NADPH oxidase. Although both p42/44 MAPK and p38 MAPK were activated rapidly in cells stimulated with BzATP, only pharmacological inhibition of p38 MAPK attenuated O(2)(-)* production. Furthermore, an inhibitor of phosphatidylinositol 3-kinase attenuated O(2)(-)* production to a greater extent than an inhibitor of p38 MAPK. Both ATP and BzATP stimulated microglia-induced cortical cell death indicating this pathway may contribute to neurodegeneration. Consistent with this hypothesis, P2X(7) receptor was specifically up-regulated around beta-amyloid plaques in a mouse model of Alzheimer's disease (Tg2576).
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There is enrichment of P2X7-positive microglia around senile plaques in human AD postmortem brain samples and AD mouse models.
“Mounting evidence has shown that there is an enrichment of P2X7-positive microglia around the senile plaques in human AD postmortem brain samples and AD mouse model.379,380”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [379]
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- Authors
- Parvathenani, L. K., Tertyshnikova, S., Greco, C. R., Roberts, S. B., Robertson, B., & Posmantur, R.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- Corresponding author
- Parvathenani, Lav K.
- ORCID
- Robertson, Barbara
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 278
- Issue
- 15
- Pages
- 13309-13317
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2153177211
- Cited by
- 488
- References
- 0
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 17 · 2023: 22 · 2022: 17 · 2021: 27 · 2020: 20 · 2019: 19 · 2018: 22 · 2017: 23 · 2016: 21 · 2015: 21 · 2014: 20 · 2013: 25 · 2012: 26
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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, superoxide production, microglia, purinergic signaling, ATP, BzATP, NADPH oxidase, p38 MAPK, phosphatidylinositol 3-kinase, neurodegeneration, amyloid plaques, Alzheimer's disease
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Adenosine Triphosphate, Alzheimer Disease, Animals, Animals, Newborn, Calcium, Cerebral Cortex, Chromones, Disease Models, Animal, Embryo, Mammalian, Enzyme Inhibitors, Female, Humans, Kinetics, Mice, Transgenic, Morpholines, Neutrophils, Pregnancy, Superoxides, Up-Regulation, Rats, Sprague-Dawley, Microglia, Receptors, Purinergic P2, NADPH Oxidases, MAP Kinase Signaling System, Mice, Rats, Receptors, Purinergic P2X7
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