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Fox Foundation for Parkinson\u2019s Research","doi-asserted-by":"publisher","award":["16561"],"award-info":[{"award-number":["16561"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease and related synucleinopathies are characterized by the abnormal accumulation of alpha-synuclein aggregates, loss of dopaminergic neurons, and gliosis of the substantia nigra. Although clinical evidence and in vitro studies indicate disruption of the Blood-Brain Barrier in Parkinson\u2019s disease, the mechanisms mediating the endothelial dysfunction is not well understood. Here we leveraged the Organs-on-Chips technology to develop a human Brain-Chip representative of the substantia nigra area of the brain containing dopaminergic neurons, astrocytes, microglia, pericytes, and microvascular brain endothelial cells, cultured under fluid flow. Our \u03b1Syn fibril-induced model was capable of reproducing several key aspects of Parkinson\u2019s disease, including accumulation of phosphorylated \u03b1Syn (pSer129-\u03b1Syn), mitochondrial impairment, neuroinflammation, and compromised barrier function. This model may enable research into the dynamics of cell-cell interactions in human synucleinopathies and serve as a testing platform for target identification and validation of novel therapeutics.<\/jats:p>","DOI":"10.1038\/s41467-021-26066-5","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T03:03:53Z","timestamp":1633748633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":232,"title":["Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6684-356X","authenticated-orcid":false,"given":"Iosif","family":"Pediaditakis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-5490","authenticated-orcid":false,"given":"Konstantia R.","family":"Kodella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-198X","authenticated-orcid":false,"given":"Dimitris V.","family":"Manatakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Y.","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris D.","family":"Hinojosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tien-Street","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias S.","family":"Manolakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-9953","authenticated-orcid":false,"given":"Kostas","family":"Vekrellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine A.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8258-7460","authenticated-orcid":false,"given":"Lorna","family":"Ewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-841X","authenticated-orcid":false,"given":"Lee L.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Karalis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"26066_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.nbd.2017.07.018","volume":"109","author":"C Peng","year":"2018","unstructured":"Peng, C., Gathagan, R. 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