guest ::
| Home > Publications Database > New P2X7 receptor function highlighted in a mouse model of Alzheimer's disease. |
| Home > Publications Database > New P2X7 receptor function highlighted in a mouse model of Alzheimer's disease. |
| Abstract/Journal Article | DZNE-2020-00666 |
;
2018
Abstract: Alzheimer’s disease (AD) is the most common form of dementia. This neurodegenerative disease is characterized by two main lesions: neurofibrillary tangles and senile plaques, composed of extracellular aggregates of amyloid β (Aβ) peptides. These peptides might act as an essential trigger for glial cell activation and the release of ATP, leading to purinergic receptors stimulation. Among purinergic receptors, the P2X7 receptor (P2X7R) was reported to be upregulated near Aβ plaques in animal models of AD and in patients with AD (Parvathenani LK et al. J Biol Chem. 2003; McLarnon JG et al. J Neuropathol Exp Neurol. 2006). 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 (Ferrari D et al. J Immunol. 2006; Sanz JM et al. J Immunol. 2009) but is also involved in APP processing (Delarasse C et al. J Biol Chem. 2011; Darmellah A et la. J Biol Chem. 2012; Diaz-Hernandez JI et al. Neurobiol Aging. 2012). Moreover, the effects of P2X7R inhibition on cognitive deficits during AD stay an unanswered question, which stress the need for further in-depth study of the role of P2X7R in AD. In the present work, we evaluated the impact of the lack of P2X7R expression in APPPS1 mice, a well-characterized mouse model of AD that develops Aβ brain lesions (Radde R et al. EMBO Rep. 2006). We examined, in detail, the potential role of P2X7R in AD pathological processes: memory and synaptic impairment, neuropathological alterations, APP processing and immune response. We found that P2X7R deficiency decreased Aβ load and also rescued cognitive deficits in mouse model of AD. In addition, we found that lack of P2X7R did not significantly affect the release of IL-1β and the APP processing in the AD mouse model. Furthermore, we highlight a novel function of P2X7R in chemokine release associated with pathogenic T-cells recruitment during Aβ pathology. In conclusion, our work supports the notion that P2X7R may be a promising therapeutic target for AD. This work was supported by grants from Agence Nationale pour la Recherche (ANR-12-MALZ-0003-02-P2X7RAD), Association France Alzheimer and Bpifrance. Our laboratory is also supported by Inserm, CNRS, Sorbonne Université and the “Investissements d'avenir” program ANR-10-IAIHU-06 (IHU-A-ICM).
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Springer ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection
|
The record appears in these collections: |
