Progressive remodeling of global protein interaction networks in a mouse model of tauopathy.

Dynamic rewiring of protein interaction networks occurs over time in a mouse model of tauopathy, with phosphorylation-dependent shifts in protein interactomes observed during disease progression.

• Why it matters: Understanding how protein networks change in neurodegenerative diseases can reveal early mechanisms of pathology and identify potential therapeutic targets.
• What they did: The study used co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to create a temporally resolved map of protein complex remodeling in a tauopathy mouse model, focusing on phosphorylation-dependent interactions.
• The result: The interactomic atlas uncovers how phosphorylation influences protein complex composition and function, highlighting network instability that develops during tauopathy and providing a framework for dissecting mechanisms of neurodegeneration.