P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice.

ABSTRACT:

Background

Neuronal accumulation of misfolded microtubule-associated protein tau is a hallmark of neuropathology in Alzheimer's disease, frontotemporal dementia, and other tauopathies, and has been a therapeutic target. Microglia can spread tau pathology by secreting tau-containing exosomes, although the specific molecular target is yet to be identified for the therapeutic intervention. P2X purinoceptor 7 (P2RX7) is an ATP-gated cation channel, enriched in microglia and triggers exosome secretion. The purpose of the study is to examine the therapeutic effect of an orally applicable, CNS-penetrant P2RX7 specific inhibitor on the early disease stage of a tauopathy mouse model.

Methods

Three-months-old P301S tau mice were treated with P2RX7-specific inhibitor GSK1482160 or vehi

SUBMITTER: Ruan Z 

PROVIDER: S-EPMC7436984 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature