P2X₇R influences tau aggregate burden in human tauopathies and shows distinct signalling in microglia and astrocytes.

ABSTRACT: The purinoceptor P2X₇R is a promising therapeutic target for tauopathies, including Alzheimer's disease (AD). Pharmacological inhibition or genetic knockdown of P2X₇R ameliorates cognitive deficits and reduces pathological tau burden in mice that model aspects of tauopathy, including mice expressing mutant human frontotemporal dementia (FTD)-causing forms of tau. However, disagreements remain over which glial cell types express P2X₇R and therefore the mechanism of action is unresolved. Here, we show that P2X₇R protein levels increase in human AD post-mortem brain, in agreement with an upregulation of P2RX7 mRNA observed in transcriptome profiles from the AMP-AD consortium. P2X₇R protein increases mirror advancing Braak stage and coinci

SUBMITTER: Beltran-Lobo P 

PROVIDER: S-EPMC10896738 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature