219: Multi-omic mapping of lipid dysregulation in Parkinson’s brain

️Episode 219: Multi-omic mapping of lipid dysregulation in Parkinson’s brain In this episode of PaperCast Base by Base, we explore Targeted multi-region lipidomics with proteomic and mitochondrial data reveals region- and stage-specific lipid alterations in Parkinson’s disease that converge on mitochondrial dysfunction Study Highlights: The study quantified 146 lipid species across eight anatomically distinct post-mortem brain regions in controls and mid- and late-stage Parkinson’s disease using targeted LC-MS/MS and integrated proteomics and mitochondrial assays. Control brains showed distinct regional lipid signatures and age-associated increases in hexosylceramides, while PD brains exhibited cortical elevations of gangliosides, HexCer and Hex2Cer and subcortical reductions of glycosphingolipids alongside increased sphingolipids and decreased phospholipids. The putamen displayed the most pronounced mid-stage changes with depletion of very long-chain ceramides and plasmalogen PE that normalized in late-stage disease, and lyso-phosphatidylcholine rose progressively with disease stage. Correlative multi-omic analysis linked sphingomyelin species to PD-related proteins and associated putaminal lipids including plasmalogens, long-chain ceramides, lyso-PC and HexCer with altered mitochondrial complex I activity. Conclusion: Region- and stage-specific lipid remodeling in Parkinson’s disease converges with mitochondrial dysfunction and identifies lipid pathways that may contribute to disease progression and therapeutic targeting Music: Enjoy the music based on this article at the end of the episode. Reference: Hällqvist J, Toomey CE, Pinto R, Baldwin T, Doykov I, Wernick A, Al Shahrani M, Evans JR, Lachica J, Pope S, Heales S, Eaton S, Mills K, Gandhi S & Heywood WE. Multi-omic analysis reveals lipid dysregulation associated with mitochondrial dysfunction in Parkinson’s disease brain. Nature Communications. 2025;16:10490. https://doi.org/10.1038/s41467-025-65489-2 License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com Castos player https://basebybase.castos.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

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