New role of P2X7 receptor in an Alzheimer's disease mouse model
| العنوان: | New role of P2X7 receptor in an Alzheimer's disease mouse model |
|---|---|
| المؤلفون: | Cécile Delarasse, Carine Dalle, Benoît Delatour, Annett Halle, Elodie Martin, Majid Amar, Jean Kanellopoulos, Véronique Sazdovitch, Bertrand Fontaine, Matthias Brückner, Ihsen Youssef, Annick Prigent, Céline Boucher, Caroline Le Duigou |
| المساهمون: | Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Max Planck Research Group Neuroanatomy and Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie |
| المصدر: | Molecular Psychiatry Molecular Psychiatry, Nature Publishing Group, In press, ⟨10.1038/s41380-018-0108-3⟩ Molecular psychiatry 24(1), 108-125 (2018). doi:10.1038/s41380-018-0108-3 Molecular Psychiatry, In press, ⟨10.1038/s41380-018-0108-3⟩ |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Inflammasomes, Physiology, metabolism [NLR Family, Pyrin Domain-Containing 3 Protein], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Interleukin-1beta, genetics [Interleukin-1beta], genetics [Alzheimer Disease], Diseases, metabolism [Receptors, Purinergic P2X7], APP protein, human, P2rx7 protein, mouse, Chemokine receptor, Amyloid beta-Protein Precursor, Mice, 0302 clinical medicine, metabolism [Amyloid beta-Protein Precursor], Amyloid precursor protein, Receptor, biology, Chemistry, Purinergic receptor, Inflammasome, Cell biology, Psychiatry and Mental health, genetics [Receptors, Purinergic P2X7], genetics [Amyloid beta-Protein Precursor], Cytokines, Cell activation, metabolism [Alzheimer Disease], medicine.drug, Mice, Transgenic, Neuroprotection, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, metabolism [Interleukin-1beta], Alzheimer Disease, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, ddc:610, P2RX7 protein, human, Molecular Biology, metabolism [Cytokines], Disease Models, Animal, 030104 developmental biology, Synaptic plasticity, biology.protein, Receptors, Purinergic P2X7, metabolism [Inflammasomes], 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | International audience; Extracellular aggregates of amyloid β (Aβ) peptides, which are characteristic of Alzheimer’s disease (AD), act as an essential trigger for glial cell activation and the release of ATP, leading to the stimulation of purinergic receptors, especially the P2X7 receptor (P2X7R). However, the involvement of P2X7R in the development of AD is still ill-defined regarding the dual properties of this receptor. Particularly, P2X7R activates the NLRP3 inflammasome leading to the release of the pro-inflammatory cytokine, IL-1β; however, P2X7R also induces cleavage of the amyloid precursor protein generating Aβ peptides or the neuroprotective fragment sAPPα. We thus explored in detail the functions of P2X7R in AD transgenic mice. Here, we show that P2X7R deficiency reduced Aβ lesions, rescued cognitive deficits and improved synaptic plasticity in AD mice. However, the lack of P2X7R did not significantly affect the release of IL-1β or the levels of non-amyloidogenic fragment, sAPPα, in AD mice. Instead, our results show that P2X7R plays a critical role in Aβ peptide-mediated release of chemokines, particularly CCL3, which is associated with pathogenic CD8+ T cell recruitment. In conclusion, our study highlights a novel detrimental function of P2X7R in chemokine release and supports the notion that P2X7R may be a promising therapeutic target for AD. |
| وصف الملف: | application/pdf |
| تدمد: | 1476-5578 1359-4184 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d470686cb1fd57d884fafdbcb97cb35b https://pubmed.ncbi.nlm.nih.gov/29934546 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d470686cb1fd57d884fafdbcb97cb35b |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765578 13594184 |
|---|