{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:37Z","timestamp":1787029057674,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["075615\/Z\/04\/z"],"award-info":[{"award-number":["075615\/Z\/04\/z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009409","name":"Russian Science Support Foundation","doi-asserted-by":"publisher","award":["19-14-00064"],"award-info":[{"award-number":["19-14-00064"]}],"id":[{"id":"10.13039\/100009409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson\u2019s disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with \u03b3-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.<\/jats:p>","DOI":"10.3390\/molecules26113078","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:01:20Z","timestamp":1621814480000},"page":"3078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Triple-Knockout, Synuclein-Free Mice Display Compromised Lipid Pattern"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2664-9145","authenticated-orcid":false,"given":"Irina A.","family":"Guschina","sequence":"first","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8570-5648","authenticated-orcid":false,"given":"Natalia","family":"Ninkina","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK"},{"name":"Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), 1 Severniy Proezd, Chernogolovka 142432, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Roman","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK"},{"name":"Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), 1 Severniy Proezd, Chernogolovka 142432, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Pokrovskiy","sequence":"additional","affiliation":[{"name":"Research Institute of Living Systems Pharmacology, Belgorod State National Research University, 85 Pobedy Street, Belgorod 308015, Belgorod Oblast, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir L.","family":"Buchman","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK"},{"name":"Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), 1 Severniy Proezd, Chernogolovka 142432, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3002.1","DOI":"10.1186\/gb-2001-3-1-reviews3002","article-title":"The synucleins","volume":"3","author":"George","year":"2001","journal-title":"Gen. 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