Opposing Regulation of Tau Condensation by Phosphorylation Levels and Molecular Chaperone Interactions

Phosphorylation patterning of Tau enhances droplet-formation propensity and modulates fibrillation, while Bri2 BRICHOS shifts Tau phase boundaries and inhibits fibril formation regardless of phosphorylation degree.

• Why it matters: Tau condensation into insoluble deposits underlies neurodegenerative tauopathies, but how phosphorylation levels and chaperone-like interactions jointly regulate the transition remains unclear.
• What they did: The study examined Tau phase separation and aggregation behavior and used solution NMR to map Bri2 BRICHOS binding on pTau in both dilute and droplet states.
• The result: Bri2 BRICHOS generally counteracts the dense phase and suppresses fibril formation, implying chaperone-based inhibitors could target biomolecular condensation and fibrillation in tauopathies.

AI summary of the abstract · may contain errors · not medical advice · read the paper.