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Triple-knockout, synuclein-free mice display compromised lipid pattern

Guschina, Irina A., Ninkina, Natalia ORCID:, Roman, Andrei, Pokrovskiy, Mikhail V. and Buchman, Vladimir L. ORCID: 2021. Triple-knockout, synuclein-free mice display compromised lipid pattern. Molecules 26 (11) , 3078. 10.3390/molecules26113078

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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’s 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 γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).
Publisher: MDPI
ISSN: 1420-3049
Funders: Wellcome Trust
Date of First Compliant Deposit: 19 July 2021
Date of Acceptance: 11 May 2021
Last Modified: 23 May 2023 20:11

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