Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-7995
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) |
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![]() | generation_of_aggregation_pro-20220925161934998.pdf | 1.78 MB | Adobe PDF | View/Open |