2025
Myelin–axon interface vulnerability in Alzheimer’s disease revealed by subcellular proteomics and imaging of human and mouse brain
Cai Y, Pinheiro-de-Sousa I, Slobodyanyuk M, Chen F, Huynh T, Kanyo J, Tang P, Fuentes L, Braker A, Welch R, Huttner A, Tong L, Yuan P, Lam T, Petsalaki E, Reimand J, Nairn A, Grutzendler J. Myelin–axon interface vulnerability in Alzheimer’s disease revealed by subcellular proteomics and imaging of human and mouse brain. Nature Neuroscience 2025, 28: 1418-1435. PMID: 40514588, PMCID: PMC12395420, DOI: 10.1038/s41593-025-01973-8.Peer-Reviewed Original ResearchSubcellular proteomicsAlzheimer's diseaseFemale 5XFAD miceProteomic hitsSubcellular localizationAmyloid-bProtein aggregationLigand-receptor interactionsAD donorsLipid metabolismExpansion microscopyPostmortem human brainProteomicsAxonal outgrowthMouse brainAlzheimerNeuronal plasticityCritical sitesAberrant myelinationMyelin ensheathmentDystrophic axonsMetabolic supportMiceAxonal structureMetabolismSubcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease
Cai Y, Kanyo J, Wilson R, Bathla S, Cardozo P, Tong L, Qin S, Fuentes L, Pinheiro-de-Sousa I, Huynh T, Sun L, Mansuri M, Tian Z, Gan H, Braker A, Trinh H, Huttner A, Lam T, Petsalaki E, Brennand K, Nairn A, Grutzendler J. Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease. Nature Aging 2025, 5: 504-527. PMID: 40065072, PMCID: PMC11922768, DOI: 10.1038/s43587-025-00823-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProximity labeling approachIPSC-derived neuronsSubcellular proteomicsCytoskeleton dynamicsPhosphorylated mTOR levelsDystrophic neuritesLipid transportBiological processesProtein turnoverAD modelHuman induced pluripotent stem cellsAmyloid depositsIPSC modelsProteomicsInduced pluripotent stem cellsPluripotent stem cellsMTOR inhibitionTherapeutic targetAxonal pathologyLabeling approachMTOR levelsMouse brainSpheroid formationAlzheimer
2022
Capillary Electrophoresis Mass Spectrometry for Scalable Single-Cell Proteomics
Shen B, Pade L, Choi S, Muñoz-LLancao P, Manzini M, Nemes P. Capillary Electrophoresis Mass Spectrometry for Scalable Single-Cell Proteomics. Frontiers In Chemistry 2022, 10: 863979. PMID: 35464213, PMCID: PMC9024316, DOI: 10.3389/fchem.2022.863979.Peer-Reviewed Original ResearchHigh-resolution mass spectrometryCapillary electrophoresisElectrospray ionization (ESISingle-cell proteomicsMass spectrometryCapillary electrophoresis mass spectrometryNano-flow liquid chromatographySample preparationSingle-cell technologiesSample amountCapillary microsamplingSubcellular proteomicsCellular dimensionsLiquid chromatographyMidline cellsSpectrometryProteomicsSubcellular analysisProtein groupsProteinMouse hippocampusSerial dilutionProtein digestibilityESINeurons
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