New role of P2X7 receptor in an Alzheimer's disease mouse model.
Alzheimer Disease
/ genetics
Amyloid beta-Protein Precursor
/ genetics
Animals
Cytokines
/ metabolism
Disease Models, Animal
Humans
Inflammasomes
/ metabolism
Interleukin-1beta
/ genetics
Mice
Mice, Transgenic
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Receptors, Purinergic P2X7
/ genetics
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
09
10
2017
accepted:
05
06
2018
revised:
14
05
2018
pubmed:
24
6
2018
medline:
7
1
2020
entrez:
24
6
2018
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 29934546
doi: 10.1038/s41380-018-0108-3
pii: 10.1038/s41380-018-0108-3
pmc: PMC6756107
doi:
Substances chimiques
APP protein, human
0
Amyloid beta-Protein Precursor
0
Cytokines
0
Inflammasomes
0
Interleukin-1beta
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
P2RX7 protein, human
0
P2rx7 protein, mouse
0
Receptors, Purinergic P2X7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108-125Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-12-MALZ-0003-02-P2X7RAD
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-12-MALZ-0003-02-P2X7RAD
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-12-MALZ-0003-02-P2X7RAD
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-IAIHU-06
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-IAIHU-06
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-12-MALZ-0003-02-P2X7RAD
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-12-MALZ-0003-02-P2X7RAD
Pays : International
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-12-MALZ-0003-02-P2X7RAD
Pays : International
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