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http://doi.org/10.25358/openscience-8251
Autoren: | Marengo, Liana Armbrust, Fred Schoenherr, Caroline Storck, Steffen E. Schmitt, Ulrich Zampar, Silvia Wirths, Oliver Altmeppen, Hermann Glatzel, Markus Kaether, Christoph Weggen, Sascha Becker-Pauly, Christoph Pietrzik, Claus U. |
Titel: | Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer’s disease |
Online-Publikationsdatum: | 6-Dez-2022 |
Erscheinungsdatum: | 2022 |
Sprache des Dokuments: | Englisch |
Zusammenfassung/Abstract: | β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) is the major described β-secretase to generate Aβ peptides in Alzheimer’s disease (AD). However, all therapeutic attempts to block BACE1 activity and to improve AD symptoms have so far failed. A potential candidate for alternative Aβ peptides generation is the metalloproteinase meprin β, which cleaves APP predominantly at alanine in p2 and in this study we can detect an increased meprin β expression in AD brain. Here, we report the generation of the transgenic APP/lon mouse model of AD lacking the functional Mep1b gene (APP/lon × Mep1b−/−). We examined levels of canonical and truncated Aβ species using urea-SDS-PAGE, ELISA and immunohistochemistry in brains of APP/lon mouse × Mep1b−/−. Additionally, we investigated the cognitive abilities of these mice during the Morris water maze task. Aβ1-40 and 1–42 levels are reduced in APP/lon mice when meprin β is absent. Immunohistochemical staining of mouse brain sections revealed that N-terminally truncated Aβ2–x peptide deposition is decreased in APP/lon × Mep1b−/− mice. Importantly, loss of meprin β improved cognitive abilities and rescued learning behavior impairments in APP/lon mice. These observations indicate an important role of meprin β within the amyloidogenic pathway and Aβ production in vivo. |
DDC-Sachgruppe: | 610 Medizin 610 Medical sciences |
Veröffentlichende Institution: | Johannes Gutenberg-Universität Mainz |
Organisationseinheit: | FB 04 Medizin |
Veröffentlichungsort: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-8251 |
Version: | Published version |
Publikationstyp: | Zeitschriftenaufsatz |
Nutzungsrechte: | CC BY |
Informationen zu den Nutzungsrechten: | https://creativecommons.org/licenses/by/4.0/ |
Zeitschrift: | Cellular and molecular life sciences 79 |
Seitenzahl oder Artikelnummer: | 168 |
Verlag: | Springer International Publishing AG |
Verlagsort: | Cham (ZG) |
Erscheinungsdatum: | 2022 |
ISSN: | 1420-9071 |
DOI der Originalveröffentlichung: | 10.1007/s00018-022-04205-5 |
Enthalten in den Sammlungen: | DFG-491381577-H |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
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meprin__knockout_reduces_brai-20221110131454718.pdf | 2.55 MB | Adobe PDF | Öffnen/Anzeigen |