Gutenberg Open Science: Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer’s disease

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8251

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DC Field	Value	Language
dc.contributor.author	Marengo, Liana	-
dc.contributor.author	Armbrust, Fred	-
dc.contributor.author	Schoenherr, Caroline	-
dc.contributor.author	Storck, Steffen E.	-
dc.contributor.author	Schmitt, Ulrich	-
dc.contributor.author	Zampar, Silvia	-
dc.contributor.author	Wirths, Oliver	-
dc.contributor.author	Altmeppen, Hermann	-
dc.contributor.author	Glatzel, Markus	-
dc.contributor.author	Kaether, Christoph	-
dc.contributor.author	Weggen, Sascha	-
dc.contributor.author	Becker-Pauly, Christoph	-
dc.contributor.author	Pietrzik, Claus U.	-
dc.date.accessioned	2022-12-06T11:29:18Z	-
dc.date.available	2022-12-06T11:29:18Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8267	-
dc.description.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.	en_GB
dc.description.sponsorship	Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer’s disease	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8251	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Cellular and molecular life sciences	de
jgu.journal.volume	79	de
jgu.pages.alternative	168	de
jgu.publisher.year	2022	-
jgu.publisher.name	Springer International Publishing AG	de
jgu.publisher.place	Cham (ZG)	de
jgu.publisher.issn	1420-9071	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1007/s00018-022-04205-5	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-H

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