{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:02:33Z","timestamp":1792116153996,"version":"4.4.0"},"reference-count":71,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sigrid Juselius Foundation"},{"name":"Doctoral Programme for Molecular Medicine"},{"name":"Finnish Cultural Foundation"},{"name":"Business Finland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The blood\u2013brain barrier (BBB) serves as an interface between the bloodstream and the central nervous system. It limits the movement of molecules and immune cells, regulates the entry of nutrients, and removes waste products from the brain. The dysfunction of the BBB has been identified in Parkinson\u2019s disease (PD) but the role of the BBB and endothelial cells (ECs) has not been well studied. LRRK2 G2019S mutation is the most common PD causing mutation with similar pathophysiology than in sporadic cases. How the mutation affects EC function has not been investigated previously in patient cells. In the study, we used iPSC-derived ECs from PD patients with the LRRK2 mutation as well as cells from healthy individuals. We report that PD patients\u2019 ECs have higher levels of \u03b1-synuclein and an decreased maximal and ATP-linked respiration and altered response to inflammatory exposure, especially to TNF\u03b1. In addition, transcriptomic analysis showed upregulation of fatty-acid-synthesis-related pathways in PD patients\u2019 ECs and the downregulation of lncRNA MEG3, both of which have been associated with PD. Altogether, PD patients\u2019 ECs manifest some of the PD-related hallmarks and are likely to contribute to the pathogenesis of PD.<\/jats:p>","DOI":"10.3390\/ijms252312874","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T03:50:57Z","timestamp":1733111457000},"page":"12874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["LRRK2 G2019S Mutated iPSC-Derived Endothelial Cells Exhibit Increased \u03b1-Synuclein, Mitochondrial Impairment, and Altered Inflammatory Responses"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8833-4106","authenticated-orcid":false,"given":"Tuuli-Maria","family":"Sonninen","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanni","family":"Peltonen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2917-7873","authenticated-orcid":false,"given":"Jonna","family":"Niskanen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5102-0672","authenticated-orcid":false,"given":"Riikka H.","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Koistinaho","sequence":"additional","affiliation":[{"name":"Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Drug Research Program, Division of Pharmacology and Pharmacotherapy, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-9414","authenticated-orcid":false,"given":"\u0160\u00e1rka","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland"},{"name":"Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Parkinson\u2019s Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"124","author":"Tysnes","year":"2017","journal-title":"J. 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