Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations

Autor: Johanna Wanngren, Patricia Lara, Karin Öjemalm, Silvia Maioli, Nasim Moradi, Lu Chen, Lars O. Tjernberg, Johan Lundkvist, IngMarie Nilsson, Helena Karlström

Publikováno v: FEBS Open Bio, Vol 4, Iss C, Pp 393-406 (2014)

The enzyme complex γ-secretase generates amyloid β-peptide (Aβ), a 37–43-residue peptide associated with Alzheimer disease (AD). Mutations in presenilin 1 (PS1), the catalytical subunit of γ-secretase, result in familial AD (FAD). A unifying th

Externí odkaz: https://doaj.org/article/d575a72492234136bf2c6d4143b2d91f

Mouse brain proteomics establishes MDGA1 and CACHD1 as in vivo substrates of the Alzheimer protease BACE1

Autor: Rohit Kumar, Julia Herber, Peter Jedlicka, Jakob Klotz, Jasenka Rudan Njavro, Bastian Dislich, Peer-Hendrik Kuhn, Regina Feederle, Stephan A. Müller, Marcus Conrad, Andreas Vlachos, Stylianos Michalakis, Stefan F. Lichtenthaler, Johanna Wanngren, Wolfgang Wurst, Thomas Koeglsperger, Merav D. Shmueli

Publikováno v: Rudan Njavro, Jasenka; Klotz, Jakob; Dislich, Bastian; Wanngren, Johanna; Shmueli, Merav D; Herber, Julia; Kuhn, Peer-Hendrik; Kumar, Rohit; Koeglsperger, Thomas; Conrad, Marcus; Wurst, Wolfgang; Feederle, Regina; Vlachos, Andreas; Michalakis, Stylianos; Jedlicka, Peter; Müller, Stephan A; Lichtenthaler, Stefan F (2020). Mouse brain proteomics establishes MDGA1 and CACHD1 as in vivo substrates of the Alzheimer protease BACE1. FASEB journal, 34(2), pp. 2465-2482. Federation of American Societies for Experimental Biology 10.1096/fj.201902347R
The FASEB journal 34(2), 2465-2482 (2020). doi:10.1096/fj.201902347R

The protease beta-site APP cleaving enzyme 1 (BACE1) has fundamental functions in the nervous system. Its inhibition is a major therapeutic approach in Alzheimer's disease, because BACE1 cleaves the amyloid precursor protein (APP), thereby catalyzing

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53c80633f97dde48d1236523da32d643

Mutations in Nicastrin Protein Differentially Affect Amyloid β-Peptide Production and Notch Protein Processing

Autor: Johanna Wanngren, Bengt Winblad, Jan Näslund, Lars O. Tjernberg, Ratan Bhat, Helena Karlström, Annelie Pamrén

Publikováno v: Journal of Biological Chemistry. 286:31153-31158

The γ-secretase complex is responsible for intramembrane processing of over 60 substrates and is involved in Notch signaling as well as in the generation of the amyloid β-peptide (Aβ). Aggregated forms of Aβ have a pathogenic role in Alzheimer di

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f565ec69feef9c25b824581a4fef8693
https://doi.org/10.1074/jbc.c111.235267

γ-secretase directly sheds the survival receptor BCMA from plasma cells

Autor: Stefanie M. Hauck, Marc Schmidt-Supprian, Frank Weber, Mohsen Khademi, Dieter E. Jenne, Qingyu Cheng, Peer-Hendrik Kuhn, Markus Krumbholz, Franziska Hoffmann, Sarah Laurent, Hartmut Wekerle, Hans-Walter Pfister, Falk Hiepe, Reinhard Hohlfeld, Yuanyuan Chu, Elisabeth Schuh, Tobias Alexander, Stefan F. Lichtenthaler, Johanna Wanngren, Tomas Olsson, Heike Rübsamen, Edgar Meinl

Publikováno v: NATURE COMMUNICATIONS
Nature Communications 6(1), 7333 (2015). doi:10.1038/ncomms8333
Nature Communications
Nat. Commun. 6:7333 (2015)

Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated by its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation by another protease

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c43b69ff255cf7ef1e718fe09db17da
https://mediatum.ub.tum.de/doc/1349641/document.pdf

Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production

Autor: Jan Ottervald, Santiago Parpal, Kia Strömberg, Johan Lundkvist, Tomas Borgegard, Johanna Wanngren, Susanne Rosqvist, Rebecka Klintenberg, Henrik Zetterberg, Jenny Blomqvist, Helena Karlström, Erik Portelius, Kaj Blennow, Anders Juréus

Publikováno v: The Journal of biological chemistry. 287(39)

The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of A�

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2851c59fed8c9e7cfa369a9c1eaddba5
https://pubmed.ncbi.nlm.nih.gov/22851182