Proteomics

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Plasma proteomics of BACE2 KO mice

ABSTRACT: The beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we performed discovery proteomics to identify substrates of the protease BACE2 in plasma of mice. Therefore, we analysed plasma from BACE2 KO, and WT controls. Inactivation of BACE2 inhibited shedding of VEGFR3/FLT4. Thus, sVEGFR3 represents a pharmacodynamic plasma marker for BACE2 activity in vivo.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Stephan Mueller  

LAB HEAD: Stefan F. Lichtenthaler

PROVIDER: PXD041579 | Pride | 2024-06-27

REPOSITORIES: Pride

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The β-secretase β-site APP cleaving enzyme (BACE1) is a central drug target for Alzheimer's disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet little is known about physiological BACE2 substrates and functions in vivo. Here, we identify BACE2 as the protease shedding the lymphangiogenic vascular endothelial growth factor receptor 3 (VEGFR3). Inactivation of BACE2, but not BACE1, inhibited shedding of VEGFR3 from primary human lymphatic endothelial  ...[more]

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