ArticleThe Journal of biological chemistry2011
The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
- From danger to resolution: targeting purinergic signaling in CNS diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- P2X7 Signaling in Neuroinflammation: Glial Crosstalk, Redox Integration, and Therapeutic Targeting.Journal of molecular neuroscience : MN · 2026Review
- Activity of Peptides Modulating the Action of p2x Receptors: Focus on the p2x7 Receptor.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Macrophage expression of P2X7 controls autoimmune uveitis.Journal of neuroinflammation · 2025Article
- The Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.Frontiers in pharmacology · 2024Review
- Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases.Frontiers in immunology · 2024Review
- Amyloid precursor protein induces reactive astrogliosis.bioRxiv : the preprint server for biology · 2023Article
- Targeting NLRP3 inflammasome for neurodegenerative disorders.Molecular psychiatry · 2023Review
- The P2X7 Receptor, a Multifaceted Receptor in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors.Neuroscience bulletin · 2023Review
- Platelets and the Role of P2X Receptors in Nociception, Pain, Neuronal Toxicity and Thromboinflammation.International journal of molecular sciences · 2022Review
- Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor.International journal of molecular sciences · 2022Review
- Review
- From purines to purinergic signalling: molecular functions and human diseases.Signal transduction and targeted therapy · 2021Review
- Antagonistic Roles of P2X7 and P2Y2 Receptors in Neurodegenerative Diseases.Frontiers in pharmacology · 2021Article
- P2XFrontiers in cellular neuroscience · 2021Review
- P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- The Role of P2X7 Receptor in Alzheimer's Disease.Frontiers in molecular neuroscience · 2020Review
- Revisiting the Idea That Amyloid-β Peptide Acts as an Agonist for P2X7.Frontiers in molecular neuroscience · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid precursor protein (APP) is cleaved by β- and γ-secretases to generate the β-amyloid (Aβ) peptides, which are present in large amounts in the amyloid plaques of Alzheimer disease (AD) patient brains. Non-amyloidogenic processing of APP by α-secretases leads to proteolytic cleavage within the Aβ peptide sequence and shedding of the soluble APP ectodomain (sAPPα), which has been reported to be endowed with neuroprotective properties. In this work, we have shown that activation of the purinergic receptor P2X7 (P2X7R) stimulates sAPPα release from mouse neuroblastoma cells expressing human APP, from human neuroblastoma cells and from mouse primary astrocytes or neural progenitor cells. sAPPα shedding is inhibited by P2X7R antagonists or knockdown of P2X7R with specific small interfering RNA (siRNA) and is not observed in neural cells from P2X7R-deficient mice. P2X7R-dependent APP-cleavage is independent of extracellular calcium and strongly inhibited by hydroxamate-based metalloprotease inhibitors, TAPI-2 and GM6001. However, knockdown of a disintegrin and metalloproteinase-9 (ADAM9), ADAM10 and ADAM17 by specific siRNA, known to have α-secretase activity, does not block the P2X7R-dependent non-amyloidogenic pathway. Using several specific pharmacological inhibitors, we demonstrate that the mitogen-activated protein kinase modules Erk1/2 and JNK are involved in P2X7R-dependent α-secretase activity. Our study suggests that P2X7R, which is expressed in hippocampal neurons and glial cells, is a potential therapeutic target in AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.