{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:40:07Z","timestamp":1784824807283,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"QBRI project IGP3, HBKU, Qatar Foundation, Doha, Qatar"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aggregation of \u03b1-synuclein (\u03b1-syn) into neurotoxic oligomers and fibrils is an important pathogenic feature of synucleinopatheis, including Parkinson\u2019s disease (PD). A further characteristic of PD is the oxidative stress that results in the formation of aldehydes by lipid peroxidation. It has been reported that the brains of deceased patients with PD contain high levels of protein oligomers that are cross-linked to these aldehydes. Increasing evidence also suggests that prefibrillar oligomeric species are more toxic than the mature amyloid fibrils. However, due to the heterogenous and metastable nature, characterization of the \u03b1-syn oligomeric species has been challenging. Here, we generated and characterized distinct \u03b1-syn oligomers in vitro in the presence of DA and lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). HNE and ONE oligomer were stable towards the treatment with SDS, urea, and temperature. The secondary structure analysis revealed that only HNE and ONE oligomers contain \u03b2-sheet content. In the seeding assay, both DA and ONE oligomers significantly accelerated the aggregation. Furthermore, all oligomeric preparations were found to seed the aggregation of \u03b1-syn monomers in vitro and found to be cytotoxic when added to SH-SY5Y cells. Finally, both HNE and ONE \u03b1-syn oligomers can be used as a calibrator in an \u03b1-syn oligomers-specific ELISA.<\/jats:p>","DOI":"10.3390\/ijms232314630","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T01:46:56Z","timestamp":1669254416000},"page":"14630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structural and Biophysical Characterization of Stable Alpha-Synuclein Oligomers"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-269X","authenticated-orcid":false,"given":"Nishant","family":"Vaikath","sequence":"first","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indulekha","family":"Sudhakaran","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-3338","authenticated-orcid":false,"given":"Ilham","family":"Abdi","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Gupta","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Majbour","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houari","family":"Abdesselem","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostas","family":"Vekrellis","sequence":"additional","affiliation":[{"name":"Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8084","authenticated-orcid":false,"given":"Omar","family":"El-Agnaf","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/S1353-8020(13)70017-8","article-title":"\u03b1-Synucleinopathy Phenotypes","volume":"20","author":"McCann","year":"2014","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13024-020-00368-6","article-title":"Initiation and Propagation of \u03b1-Synuclein Aggregation in the Nervous System","volume":"15","author":"Hijaz","year":"2020","journal-title":"Mol. 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