PI3K-AKT activation resculpts integrin signaling to drive filamentous tau-induced proinflammatory astrogliosis.

ABSTRACT: Background Microtubule-binding protein tau is a misfolding-prone protein associated with tauopathies. As tau undergoes cell-to-cell transmission, extracellular tau aggregates convert astrocytes into a pro-inflammatory state via integrin activation, causing them to release unknown neurotoxic factors. Results Here, we combine transcriptomics with isotope labeling-based quantitative mass spectrometry analysis of mouse primary astrocyte secretome to establish PI3K-AKT as a critical differentiator between pathogenic and physiological integrin activation; simultaneous activation of PI3K-AKT and focal adhesion kinase (FAK) in tau fibril-treated astrocytes changes the output of integrin signaling, causing pro-inflammatory gene upregulation, trans-Golgi network restructuring, and altered secretory

SUBMITTER: Wang P 

PROVIDER: S-EPMC10479431 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature