Selenoprotein P is a target for regulating extracellular vesicle biogenesis and secretion from activated microglia in vivo.

ABSTRACT: Microglia, brain innate immune cells, participate in the spread of inflammatory signals and aggregated proteins through secretion of extracellular vesicles (EVs). Selenoprotein P (Sepp1) is a potential regulator of microglial EV secretion. Here, we investigate the effect of Sepp1 silencing on microglial transcriptomics to elucidate the Sepp1 regulatory mechanism of EV secretion and validate this effect in APP^NL-G-F knockin mice. Silencing of Sepp1 significantly reduces EV secretion and CD63 loading to EVs from BV-2 microglia, as determined by single-vesicle flow cytometry and super-resolution microscopy. Sepp1 deficiency downregulates EV biogenesis machinery, accompanied by increased lysosomal activity and lipid metabolism. Silencing of Sepp1 in astrocytes but not neurons suppre

SUBMITTER: Bodart-Santos V 

PROVIDER: S-EPMC11834494 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature