{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:11:04Z","timestamp":1791943864605,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-20146-p"],"award-info":[{"award-number":["19-74-20146-p"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease, associated with mutations in the GBA1 gene (GBA1-PD), is the most common genetic form of Parkinson\u2019s disease (PD), marked by clinical heterogeneity influenced by mutation type. Extracellular vesicles (EVs), key mediators of intercellular communication, are implicated in PD pathogenesis through the transport of pathological proteins and lipids. In this study, we analyzed blood plasma-derived EVs from GBA1-PD patients carrying p.N370S and p.L444P mutations and from healthy controls using cryo-electron microscopy, lipidomics, and proteomics. EVs from GBA1-PD patients were significantly larger than those from controls, with the largest size and most multilayered vesicles observed in p.N370S carriers. Lipidomic profiling identified 237 lipid species; of these, 186 lipids were altered in p.N370S and 24 in p.L444P versus controls. Mutation carriers showed distinct lipid signatures, with p.L444P samples enriched predominantly in sphingolipids, while p.N370S carriers exhibited more extensive lipid remodeling across multiple classes, including triglycerides, cholesteryl esters, and phospholipids. Notably, Cer 23:0 was elevated across all GBA1-PD groups. Proteomic analysis revealed enrichment in pathways related to lipid transport, immune regulation, and vesicle-mediated processes. Overall, GBA1-PD patients share a distinct lipidomic EV signature, with mutation-specific patterns reflecting differing mechanisms of lysosomal dysfunction. These findings support the potential of EV profiling to unravel disease heterogeneity and identify biomarkers.<\/jats:p>","DOI":"10.3390\/ijms26189152","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T12:33:32Z","timestamp":1758285212000},"page":"9152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["p.N370S GBA1 Mutation Influences the Morphology and Lipid Composition of Extracellular Vesicles in Blood Plasma from Patients with Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-2283","authenticated-orcid":false,"given":"Tatiana S.","family":"Usenko","sequence":"first","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, Gatchina 188300, Russia"},{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint Petersburg State Medical University, St. Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena E.","family":"Kopytova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, Gatchina 188300, Russia"},{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint Petersburg State Medical University, St. Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem D.","family":"Izyumchenko","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, Gatchina 188300, Russia"},{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint Petersburg State Medical University, St. Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-0095","authenticated-orcid":false,"given":"Darya G.","family":"Kulabukhova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, Gatchina 188300, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artemiy S.","family":"Silantyev","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 143007, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-6938","authenticated-orcid":false,"given":"Victoria D.","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 143007, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-3918","authenticated-orcid":false,"given":"Katerina S.","family":"Basharova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. 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Bechtereva Institute of the Human Brain of Russian Academy of Sciences, St. Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla A.","family":"Timofeeva","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint Petersburg State Medical University, St. Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3160-2314","authenticated-orcid":false,"given":"Valentina V.","family":"Miroshnikova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. 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