Biphasic modulation of tau liquid-liquid phase separation by polyphenols

Molecular tools that modulate tau liquid-liquid phase separation (LLPS) promise to treat tauopathies. We screened a set of polyphenols and demonstrated concentration-dependent biphasic modulation of tau LLPS by gallic acid (GA), showcasing its ability to expedite the liquid-to-gel transition in tau condensates and effectively impede the formation of deleterious fibrillar aggregates. Polyphenols, notably gallic acid (GA), act as a biphasic modulator of tau liquid-liquid phase separation in a concentration-dependent manner. GA accelerates the sol-to-gel transition and inhibits tau aggregate-associated toxicity.