P2X7-deficiency improves plasticity and cognitive abilities in a mouse model of Tauopathy.
Prog Neurobiol
; 206: 102139, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34391810
ABSTRACT
Alzheimer's disease is the most common form of dementia characterized by intracellular aggregates of hyperphosphorylated Tau protein and extracellular accumulation of amyloid ß (Aß) peptides. We previously demonstrated that the purinergic receptor P2X7 (P2X7) plays a major role in Aß-mediated neurodegeneration but the relationship between P2X7 and Tau remained overlooked. Such a link was supported by cortical upregulation of P2X7 in patients with various type of frontotemporal lobar degeneration, including mutation in the Tau-coding gene, MAPT, as well as in the brain of a Tauopathy mouse model (THY-Tau22). Subsequent phenotype analysis of P2X7-deficient Tau mice revealed the instrumental impact of this purinergic receptor. Indeed, while P2X7-deficiency had a moderate effect on Tau pathology itself, we observed a significant reduction of microglia activation and of Tau-related inflammatory mediators, particularly CCL4. Importantly, P2X7 deletion ultimately rescued synaptic plasticity and memory impairments of Tau mice. Altogether, the present data support a contributory role of P2X7 dysregulation on processes governing Tau-induced brain anomalies. Due to the convergent role of P2X7 blockade in both Aß and Tau background, P2X7 inhibitors might prove to be ideal candidate drugs to curb the devastating cognitive decline in Alzheimer's disease and Tauopathies.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tauopatias
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Receptores Purinérgicos P2X7
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Revista:
Prog Neurobiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França