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
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7995
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Molecular neurodegeneration 11
Pages or article number:	Art. 19
Publisher:	BioMed Central
Publisher place:	London
Issue date:	2016
ISSN:	1750-1326
Publisher URL:	http://dx.doi.org/10.1186/s13024-016-0084-5
Publisher DOI:	10.1186/s13024-016-0084-5
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)