{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T02:54:42Z","timestamp":1781924082108,"version":"3.54.5"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":92,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"name":"North East Network Centre"},{"name":"Teesside University Seedcorn Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aggregation of \u03b1-synuclein is a central neuropathological hallmark in neurodegenerative disorders known as Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. In the aggregation process, \u03b1-synuclein transitions from its native disordered\/\u03b1-helical form to a \u03b2-sheet-rich structure, forming oligomers and protofibrils that accumulate into Lewy bodies, in a process that is thought to underlie neurodegeneration. Lipids are thought to play a critical role in this process by facilitating \u03b1-synuclein aggregation and contributing to cell toxicity, possibly through ceramide production. This study aimed to investigate biochemical changes associated with \u03b1-synuclein aggregation, focusing on lipid changes, using Raman spectroscopy coupled with machine learning. HEK293, Neuro2a and SH-SY5Y expressing increased levels of \u03b1-synuclein were treated with sonicated \u03b1-synuclein pre-formed fibrils, to model seeded aggregation. Raman spectroscopy, complemented by an in-house lipid spectral library, was used to monitor the aggregation process and its effects on cellular viability over 14 days. We detected \u03b1-synuclein aggregation by assessing \u03b2-sheet peaks at 1045\u2005cm\u207b1, in cells treated with \u03b1-synuclein pre-formed fibrils, using machine learning (principal component analysis and uniform manifold approximation and projection) analysis based on Raman spectral features. Changes in lipid profiles, and especially sphingolipids, including a decrease in sphingomyelin and increase in ceramides, were observed, consistent with oxidative stress and apoptosis. Altogether, our study informs on biochemical alterations that can be considered for the design of therapeutic strategies for Parkinson's disease and related synucleinopathies.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf133","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T19:24:44Z","timestamp":1743708284000},"source":"Crossref","is-referenced-by-count":7,"title":["Alpha-synuclein aggregation induces prominent cellular lipid changes as revealed by Raman spectroscopy and machine learning analysis"],"prefix":"10.1093","volume":"7","author":[{"given":"Nathan P","family":"Coles","sequence":"first","affiliation":[{"name":"School of Health & Life Sciences, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]},{"name":"National Horizons Centre, Teesside University , Darlington DL1 1HG 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,","place":["UK"]},{"name":"National Horizons Centre, Teesside University , Darlington DL1 1HG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Occhipinti","sequence":"additional","affiliation":[{"name":"National Horizons Centre, Teesside University , Darlington DL1 1HG ,","place":["UK"]},{"name":"School of Computing, Engineering & Digital Technologies, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]},{"name":"Centre for Digital Innovation, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-7909","authenticated-orcid":false,"given":"Claudio","family":"Angione","sequence":"additional","affiliation":[{"name":"National Horizons Centre, Teesside University , Darlington DL1 1HG ,","place":["UK"]},{"name":"School of Computing, Engineering & Digital Technologies, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]},{"name":"Centre for Digital Innovation, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Marles-Wright","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Cookson Building, Framlington Place, Newcastle University , Newcastle upon Tyne NE2 4HH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Koss","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Medicine, University of Dundee , Nethergate, Dundee DD1 4HN ,","place":["Scotland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J","family":"Thomas","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University , Newcastle upon Tyne NE2 4HH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago F","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University , Newcastle upon Tyne NE2 4HH ,","place":["UK"]},{"name":"University Medical Center G\u00f6ttingen, Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, Von-Siebold-Stra\u00dfe 3a, 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Max Planck Institute for Multidisciplinary Sciences , Am Fa\u00dfberg 11, 37077 G\u00f6ttingen ,","place":["Germany"]},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) , Von-Siebold-Stra\u00dfe 3A, 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota S","family":"Filippou","sequence":"additional","affiliation":[{"name":"School of Health & Life Sciences, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]},{"name":"National Horizons Centre, Teesside University , Darlington DL1 1HG ,","place":["UK"]},{"name":"Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki , Thessaloniki 54124 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4835-5359","authenticated-orcid":false,"given":"Ahmad A","family":"Khundakar","sequence":"additional","affiliation":[{"name":"School of Health & Life Sciences, Teesside University , Middlesbrough TS1 3BX ,","place":["UK"]},{"name":"National Horizons Centre, Teesside University , Darlington DL1 1HG ,","place":["UK"]},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University , Newcastle upon Tyne NE2 4HH 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