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Todorov-Völgyi, K.* ; González-Gallego, J.* ; Müller, S.A.* ; Beaufort, N.* ; Malik, R.* ; Schifferer, M.* ; Todorov, M.I. ; Crusius, D.* ; Robinson, S.* ; Schmidt, A.* ; Körbelin, J.* ; Bareyre, F.* ; Ertürk, A. ; Haass, C.* ; Simons, M.* ; Paquet, D.* ; Lichtenthaler, S.F.* ; Dichgans, M.*

Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.

Nature Aging 4, 595-612 (2024)
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Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis revealed a segregation of age-related protein dynamics with biological functions, including a downregulation of vesicle-mediated transport. We found a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis and lysosomal degradation. In gene deletion and overexpression experiments, Arf6 affected endocytosis pathways in endothelial cells. Our approach uncovered changes not picked up by transcriptomic studies, such as accumulation of vesicle cargo and receptor ligands, including Apoe. Proteomic analysis of BECs from Apoe-deficient mice revealed a signature of accelerated aging. Our findings provide a resource for analysing BEC function during aging.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Proteins; Age; Cells; Apoe; Dysfunction; Expression; Disease; Arf6; Consequences; Hippocampal
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2662-8465
e-ISSN 2662-8465
Journal Nature Aging
Quellenangaben Volume: 4, Issue: 4, Pages: 595-612 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505800-001
Grants Deutsche Forschungsgemeinschaft (German Research Foundation)
ERA-NET Neuron
Leducq Foundation
Vascular Dementia Research Foundation, through the Federal Ministry for Education and Research (BMBF)
Deutsche Forschungsgemeinschaft (DFG), as part of the Munich Cluster for Systems Neurology
European Innovation Council program
European Union's Horizon 2020 Research and Innovation Program SVDs@target
LMUexcellent fund
DOI 10.1038/s43587-024-00598-z
WOS ID 001190193800002
Scopus ID 85188470836
PubMed ID 38519806
Erfassungsdatum 2024-05-13
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