Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes

ABSTRACT: Secretory proteins aggregate into non-soluble dense-core granules in recycling endosome-like compartments prior to regulated release. By contrast, aberrantly processed, secreted amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) form pathological extracellular amyloidogenic aggregations in late-stage Alzheimer's disease (AD). By examining living Drosophila prostate-like secondary cells, we show that both APP and Aβ peptides affect normal biogenesis of dense-core granules. These cells generate dense-core granules and secreted nanovesicles called Rab11 exosomes via evolutionarily conserved mechanisms within highly enlarged secretory compartments with recycling endosomal identity. The fly APP homologue, APP-like (APPL), associates with these vesicles and the compartmental li

SUBMITTER: Preman, J Singh 

PROVIDER: S-SCDT-10_1038-S44318-025-00497-Y | biostudies-other |

REPOSITORIES: biostudies-other