Research ExplorerPublicationsMeprin β knockout reduces brain Aβ levels and rescues learni...

Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease

Standard

Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease. / 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.

In: CELL MOL LIFE SCI, Vol. 79, No. 3, 168, 02.03.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Marengo, L, Armbrust, F, Schoenherr, C, Storck, SE, Schmitt, U, Zampar, S, Wirths, O, Altmeppen, H, Glatzel, M, Kaether, C, Weggen, S, Becker-Pauly, C & Pietrzik, CU 2022, 'Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease', CELL MOL LIFE SCI, vol. 79, no. 3, 168. https://doi.org/10.1007/s00018-022-04205-5

APA

Marengo, L., Armbrust, F., Schoenherr, C., Storck, S. E., Schmitt, U., Zampar, S., Wirths, O., Altmeppen, H., Glatzel, M., Kaether, C., Weggen, S., Becker-Pauly, C., & Pietrzik, C. U. (2022). Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease. CELL MOL LIFE SCI, 79(3), [168]. https://doi.org/10.1007/s00018-022-04205-5

Vancouver

Marengo L, Armbrust F, Schoenherr C, Storck SE, Schmitt U, Zampar S et al. Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease. CELL MOL LIFE SCI. 2022 Mar 2;79(3). 168. https://doi.org/10.1007/s00018-022-04205-5

Bibtex

@article{6df09d7ad72c4168aeb8840cac1738f8,
title = "Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease",
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.",
keywords = "Aged, Alzheimer Disease/metabolism, Amyloid Precursor Protein Secretases/metabolism, Amyloid beta-Peptides/metabolism, Animals, Astrocytes/metabolism, Brain/metabolism, Crosses, Genetic, Disease Models, Animal, Female, Glial Fibrillary Acidic Protein/metabolism, Humans, Learning, Male, Memory Disorders/pathology, Metalloendopeptidases/deficiency, Mice, Knockout, Peptides/metabolism, Protein Processing, Post-Translational",
author = "Liana Marengo and Fred Armbrust and Caroline Schoenherr and Storck, {Steffen E} and Ulrich Schmitt and Silvia Zampar and Oliver Wirths and Hermann Altmeppen and Markus Glatzel and Christoph Kaether and Sascha Weggen and Christoph Becker-Pauly and Pietrzik, {Claus U}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = mar,
day = "2",
doi = "10.1007/s00018-022-04205-5",
language = "English",
volume = "79",
journal = "CELL MOL LIFE SCI",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "3",

}

RIS

TY - JOUR

T1 - Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer's disease

AU - Marengo, Liana

AU - Armbrust, Fred

AU - Schoenherr, Caroline

AU - Storck, Steffen E

AU - Schmitt, Ulrich

AU - Zampar, Silvia

AU - Wirths, Oliver

AU - Altmeppen, Hermann

AU - Glatzel, Markus

AU - Kaether, Christoph

AU - Weggen, Sascha

AU - Becker-Pauly, Christoph

AU - Pietrzik, Claus U

N1 - © 2022. The Author(s).

PY - 2022/3/2

Y1 - 2022/3/2

N2 - 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.

AB - 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.

KW - Aged

KW - Alzheimer Disease/metabolism

KW - Amyloid Precursor Protein Secretases/metabolism

KW - Amyloid beta-Peptides/metabolism

KW - Animals

KW - Astrocytes/metabolism

KW - Brain/metabolism

KW - Crosses, Genetic

KW - Disease Models, Animal

KW - Female

KW - Glial Fibrillary Acidic Protein/metabolism

KW - Humans

KW - Learning

KW - Male

KW - Memory Disorders/pathology

KW - Metalloendopeptidases/deficiency

KW - Mice, Knockout

KW - Peptides/metabolism

KW - Protein Processing, Post-Translational

U2 - 10.1007/s00018-022-04205-5

DO - 10.1007/s00018-022-04205-5

M3 - SCORING: Journal article

C2 - 35235058

VL - 79

JO - CELL MOL LIFE SCI

JF - CELL MOL LIFE SCI

SN - 1420-682X

IS - 3

M1 - 168

ER -