{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:41:07Z","timestamp":1790847667229,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T00:00:00Z","timestamp":1437523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute on Aging","award":["P30 AG19610"],"award-info":[{"award-number":["P30 AG19610"]}]},{"DOI":"10.13039\/100007306","name":"Arizona Department of Health Services","doi-asserted-by":"publisher","award":["211002"],"award-info":[{"award-number":["211002"]}],"id":[{"id":"10.13039\/100007306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008335","name":"Arizona Biomedical Research Commission","doi-asserted-by":"publisher","award":["4001"],"award-info":[{"award-number":["4001"]}],"id":[{"id":"10.13039\/100008335","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Misfolding and aggregation of \u03b1-synuclein into toxic soluble oligomeric \u03b1-synuclein aggregates has been strongly correlated with the pathogenesis of Parkinson\u2019s disease (PD). Here, we show that two different morphologically distinct oligomeric \u03b1-synuclein aggregates are present in human post-mortem PD brain tissue and are responsible for the bulk of \u03b1-synuclein induced toxicity in brain homogenates from PD samples. Two antibody fragments that selectively bind the different oligomeric \u03b1-synuclein variants block this \u03b1-synuclein induced toxicity and are useful tools to probe how various cell models replicate the \u03b1-synuclein aggregation pattern of human PD brain. Using these reagents, we show that mammalian cell type strongly influences \u03b1-synuclein aggregation, where neuronal cells best replicate the PD brain \u03b1-synuclein aggregation profile. Overexpression of \u03b1-synuclein in the different cell lines increased protein aggregation but did not alter the morphology of the oligomeric aggregates generated. Differentiation of the neuronal cells into a cholinergic-like or dopaminergic-like phenotype increased the levels of oligomeric \u03b1-synuclein where the aggregates were localized in cell neurites and cell bodies.<\/jats:p>","DOI":"10.3390\/biom5031634","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T08:45:40Z","timestamp":1437554740000},"page":"1634-1651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson\u2019s Disease Brains Are Differentially Generated in Mammalian Cell Models"],"prefix":"10.3390","volume":"5","author":[{"given":"Wei","family":"Xin","sequence":"first","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharareh","family":"Emadi","sequence":"additional","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Williams","sequence":"additional","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Neurology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Schulz","sequence":"additional","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"He","sequence":"additional","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Now","family":"Alam","sequence":"additional","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Neurology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sierks","sequence":"additional","affiliation":[{"name":"Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.nbd.2007.11.002","article-title":"Generation of a alpha-synuclein-based rat model of Parkinson\u2019s disease","volume":"30","author":"Recchiaa","year":"2008","journal-title":"Neurobiol. 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