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. We further show that EGCG
oxidation, tau phosphorylation, and the chemical structure of the
polyphenol influence the efficacy of EGCG in facilitating tau LLPS.
Complementary to the inhibitory activity of EGCG in tau fibrillization,
our findings provide novel insights into the biological activity of
EGCG and offer new clues for future studies on the molecular mechanism
by which EGCG alleviates neurodegenerative diseases.
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