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Open Access 01-12-2016 | Research article

Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site

Authors: Caroline Schönherr, Jessica Bien, Simone Isbert, Rielana Wichert, Johannes Prox, Hermann Altmeppen, Sathish Kumar, Jochen Walter, Stefan F. Lichtenthaler, Sascha Weggen, Markus Glatzel, Christoph Becker-Pauly, Claus U. Pietrzik

Published in: Molecular Neurodegeneration | Issue 1/2016

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.

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Title: Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
Authors: Caroline Schönherr
Jessica Bien
Simone Isbert
Rielana Wichert
Johannes Prox
Hermann Altmeppen
Sathish Kumar
Jochen Walter
Stefan F. Lichtenthaler
Sascha Weggen
Markus Glatzel
Christoph Becker-Pauly
Claus U. Pietrzik
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2016
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-016-0084-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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