(-)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid-Liquid Phase Separation of Alzheimer's-Related Protein Tau.

The microtubule-associated protein tau is involved in Alzheimer's disease and other tauopathies. Recently, tau has been shown to undergo liquid-liquid phase separation (LLPS), which is implicated in the physiological function and pathological aggregation of tau. In this report, we demonstrate that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) promotes the formation of liquid tau droplets at neutral pH by creating a network of hydrophobic interactions and hydrogen bonds, mainly with the proline-rich domain of tau.