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Authors: Schönherr, Caroline
Bien, Jessica
Isbert, Simone
Wichert, Rielana
Prox, Johannes
Altmeppen, Hermann
Kumar, Sathish
Walter, Jochen
Lichtenthaler, Stefan F.
Weggen, Sascha
Glatzel, Markus
Becker-Pauly, Christoph
Pietrzik, Claus
Title: Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
Online publication date: 14-Oct-2022
Year of first publication: 2016
Language: english
Abstract: BACKGROUND: The metalloprotease meprin β cleaves the Alzheimer's Disease (AD) relevant amyloid precursor protein (APP) as a β-secretase reminiscent of BACE-1, however, predominantly generating N-terminally truncated Aβ2-x variants. RESULTS: Herein, we observed increased endogenous sAPPα levels in the brains of meprin β knock-out (ko) mice compared to wild-type controls. We further analyzed the cellular interaction of APP and meprin β and found that cleavage of APP by meprin β occurs prior to endocytosis. The N-terminally truncated Aβ2-40 variant shows increased aggregation propensity compared to Aβ1-40 and acts even as a seed for Aβ1-40 aggregation. Additionally, we observed that different APP mutants affect the catalytic properties of meprin β and that, interestingly, meprin β is unable to generate N-terminally truncated Aβ peptides from Swedish mutant APP (APPswe). CONCLUSION: Concluding, we propose that meprin β may be involved in the generation of N-terminally truncated Aβ2-x peptides of APP, but acts independently from BACE-1.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Molecular neurodegeneration
Pages or article number: Art. 19
Publisher: BioMed Central
Publisher place: London
Issue date: 2016
ISSN: 1750-1326
Publisher URL:
Publisher DOI: 10.1186/s13024-016-0084-5
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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