Allosteric activation of a cell-type-specific GPR120 inhibits amyloid pathology of Alzheimer's disease.

ABSTRACT: Black rice diets are enriched with unsaturated fatty acids that are thought to be beneficial for neurodegenerative disorders in aging. Here we find that α-linolenic acid (ALA) and 11,14-eicosadienoic acid (EDA), which are naturally enriched in black rice, inhibit amyloid pathology, rescue cognition and extend lifespan in mouse preclinical models of Alzheimer's disease via allosteric activation of G protein-coupled receptor 120 (GPR120) in plaque-associated macrophages and activated microglia. We generate the structures of GPR120 bound to ALA and EDA. We demonstrate that ALA and EDA allosterically modulate and synergistically activate GPR120 for macrophagic phagocytosis and clearance of β-amyloid aggregates in Alzheimer's disease mice. A cell-type-specific deletion of GPR120, or Gαi1, compl

SUBMITTER: He A 

PROVIDER: S-EPMC12823430 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature