Rescue of miRNA export from amyloid-exposed astroglia by Ras homolog enriched in brain (Rheb) protein

Amyloid protein disrupts miRNA activity in astroglial cells by inducing miRNA sequestration in RNA processing bodies or P-bodies, thereby hindering extracellular vesicle-mediated intercellular communication through miRNAs. The mTOR activator Rheb facilitates miRNA recycling and export, mitigating the negative effects of amyloid on miRNA pathways. Additionally, the miRNA-binding protein Syntaxin 5 or STX5 speeds up the miRNA export process, possibly by relocating miRNPs from P-bodies. However, STX5 cannot support miRNA repressive activity or recycling in astroglia exposed to amyloid. Therefore, relocating miRNA out of P-bodies is necessary for export but not sufficient for miRNA reactivation in amyloid beta (Ab)- affected cells. Interestingly, Rheb enhances both miRNA P-body relocalization, reactivation, and export, thereby counteracting amyloid-related disruptions.