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However, efficiently delivering these therapeutic peptides to disease\u2010relevant cells within the central nervous system (CNS) remains challenging due to degradation in circulation and poor blood\u2010brain barrier and cell membrane penetration. Here, we present a strategy to use extracellular vesicles (EVs) as delivery vehicles for the therapeutic peptides to enhance their cellular uptake and CNS targeting. Following an optimized passive loading approach, we successfully packaged these peptides into EVs, improving their cellular uptake by disease\u2010relevant neural cells in vitro and brain biodistribution in mice following intravenous administration. EV\u2010based delivery enhanced the therapeutic efficacy of these peptides in disrupting FADD\u2010LRRK2 interactions, reducing downstream caspase signaling and neuronal death in cellular models of PD compared to the free peptide format. These findings support the use of EVs as a promising shuttle for peptide\u2010based therapies in PD and potentially other neurological disorders.<\/jats:p>","DOI":"10.1002\/jex2.70116","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T16:08:07Z","timestamp":1769875687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Extracellular Vesicle\u2010Mediated Delivery of Constrained Peptides Disrupts the Pathogenic Interaction of LRRK2\u2010FADD in Parkinson's Disease"],"prefix":"10.1002","volume":"5","author":[{"given":"Yaochao","family":"Zheng","sequence":"first","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Sciences University of Georgia  Athens Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian 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