Role of Testosterone Signaling in Microglia: A Potential Role for Sex-Related Differences in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is less prevalent in men than in women, although mechanisms remain unclear. Microglia degrade aggregated amyloid β (Aβ) through the lysosomal system, including autophagy. G protein-coupled receptor family C group 6 member A (GPRC6A), predominantly expressed in mouse microglial MG6 cells, is a primary mediator of testosterone signaling. This study examines testosterone's role in modulating Aβ-induced autophagy in microglia. Testosterone promotes Aβ-induced autophagy leading to Aβ clearance in MG6 cells by suppressing extracellular signal-regulated kinase (ERK) phosphorylation and subsequently inhibiting mammalian target of rapamycin (mTOR) activation, which is abrogated by shRNA knockdown of GPRC6A. In in vivo experiments with male 5xFAD AD model mice, Aβ clearance

SUBMITTER: Du H 

PROVIDER: S-EPMC12097063 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature