Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils.

ABSTRACT:

Background

Microglia play a crucial role in brain homeostasis through phagocytosis of amyloid-β (Aβ) fibrils, a hallmark of Alzheimer disease (AD) pathology. The balance between Aβ production and clearance is critical for AD pathogenesis, with impaired clearance mechanisms potentially contributing to disease progression. G-protein coupled receptor 34 (GPR34), a microglia-enriched Gi/o-coupled receptor, is highly expressed in homeostatic microglia and may regulate phagocytic functions, yet its role in Aβ clearance remains poorly understood.

Methods

Using flow cytometry-based assays, we investigated the effect of a selective GPR34 agonist (M1) on Aβ uptake in mouse primary microglia and human induced pluripotent stem cell-derived microglia. We evaluated uptake specificity acro

SUBMITTER: Etani H 

PROVIDER: S-EPMC12632051 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature