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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Proteins; Age; Cells; Apoe; Dysfunction; Expression; Disease; Arf6; Consequences; Hippocampal
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
2662-8465
e-ISSN
2662-8465
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 4,
Heft: 4,
Seiten: 595-612
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Campus, 4 Crinan St, London, N1 9xw, England
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute for Tissue Engineering and Regenerative Medicine (ITERM)
POF Topic(s)
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-505800-001
Förderungen
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
Copyright
Erfassungsdatum
2024-05-13