Glucocorticoids regulate small extracellular vesicle (sEV) release via activation of nSMase2.

ABSTRACT: Chronic stress, marked by prolonged elevation of glucocorticoid (GC) stress hormones, is a major risk factor for Alzheimer's disease (AD) and accelerates AD pathology in mouse models. A key mechanism contributing to AD progression is the release of small extracellular vesicles (sEVs) carrying pathogenic proteins (e.g., tau, amyloid-beta) between brain regions, but the role of GCs in sEV biogenesis and release is unknown. Using total internal reflection fluorescence (TIRF) microscopy and the pH-sensitive marker mCh-CD63-pHluorin to visualize sEV release, we show that GCs stimulate sEV secretion in a neuronal cell line. This process requires the GTPase Rab27a and the enzyme neutral sphingomyelinase 2 (nSMase2), which catalyzes ceramide production and drives sEV formation. We further demonstr

SUBMITTER: Burke M 

PROVIDER: S-EPMC12632620 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature