biostudies-literatureUnknown13(1)Wang PNational Institutes of Health<h4>Background</h4>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.<h4>Results</h4>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 altCell & bioscience179https://www.ebi.ac.uk/biostudies/studies/S-EPMC10536728biostudies-literaturePI3K-AKT activation resculpts integrin signaling to drive filamentous tau-induced proinflammatory astrogliosis.PMC10536728Wang PAnderson DEYe YfalsePI3K-AKT activation resculpts integrin signaling to drive filamentous tau-induced proinflammatory astrogliosis.<h4>Background</h4>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.<h4>Results</h4>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 alt2023-01-01T00:00:00Z2023 Sep2025-04-05T11:20:16.294Z2025-02-19T03:36:45.888ZS-EPMC105367283775924510.1186/s13578-023-01128-x