{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vekrellis K"],"funding":["Michael J. Fox Foundation for Parkinson's Research","National Recovery and Resilience plan, Next Generation EU","European Regional Development Fund"],"pagination":["277"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480265"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Extracellular vesicles (EVs) are nano-sized lipid vesicles released into the extracellular space. We investigated the role of mouse brain-derived EVs in α-synuclein (α-syn) degradation and pathology transmission. Using sucrose gradient isolation and biochemical characterization, we found that EVs harbor active proteases that cleave both monomeric α-syn and pre-formed fibrils (PFFs). Protease activity and inhibitor profiling identified cathepsins B and S as key enzymes mediating this cleavage. EV-mediated proteolysis reduced the seeding capacity of α-syn PFFs in vitro and in vivo, whereas protease inhibition enhanced aggregation. Proteomic analysis revealed a restricted protease repertoire within EV cargo. Our findings suggest that EVs regulate extracellular α-syn levels via proteolysis, th"],"journal":["NPJ Parkinson's disease"],"pubmed_title":["Proteolytic activities of extracellular vesicles attenuate A-synuclein aggregation."],"pmcid":["PMC12480265"],"funding_grant_id":["022676","TAEDR-0535850","Τ2ΕDK- 02813"],"pubmed_authors":["Kolianou A","Skarveli M","Kokoli M","Vekrellis K","Melachroinou K","Sotiropoulou G","Samiotaki M","Lamprokostopoulou A","Zingkou E"],"additional_accession":[]},"is_claimable":false,"name":"Proteolytic activities of extracellular vesicles attenuate A-synuclein aggregation.","description":"Extracellular vesicles (EVs) are nano-sized lipid vesicles released into the extracellular space. We investigated the role of mouse brain-derived EVs in α-synuclein (α-syn) degradation and pathology transmission. Using sucrose gradient isolation and biochemical characterization, we found that EVs harbor active proteases that cleave both monomeric α-syn and pre-formed fibrils (PFFs). Protease activity and inhibitor profiling identified cathepsins B and S as key enzymes mediating this cleavage. EV-mediated proteolysis reduced the seeding capacity of α-syn PFFs in vitro and in vivo, whereas protease inhibition enhanced aggregation. Proteomic analysis revealed a restricted protease repertoire within EV cargo. Our findings suggest that EVs regulate extracellular α-syn levels via proteolysis, th","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T23:01:32.506Z","creation":"2026-05-02T03:12:12.366Z"},"accession":"S-EPMC12480265","cross_references":{"pubmed":["41022736"],"doi":["10.1038/s41531-025-01122-9"]}}