Literature DB >> 10405162

A novel substrate for analyzing Alzheimer's disease gamma-secretase.

S F Lichtenthaler1, G Multhaup, C L Masters, K Beyreuther.   

Abstract

Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by beta-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called gamma-secretase. To study the enzymatic properties of gamma-secretase independently of beta-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by gamma-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals showing amyloid pathology.

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Year:  1999        PMID： 10405162     DOI： 10.1016/s0014-5793(99)00730-9

Source DB:  PubMed          Journal:  FEBS Lett        ISSN： 0014-5793            Impact factor:   4.124


  21 in total

1.  Lysine 624 of the amyloid precursor protein (APP) is a critical determinant of amyloid β peptide length: support for a sequential model of γ-secretase intramembrane proteolysis and regulation by the amyloid β precursor protein (APP) juxtamembrane region.

Authors:  Thomas L Kukar; Thomas B Ladd; Paul Robertson; Sean A Pintchovski; Brenda Moore; Maralyssa A Bann; Zhao Ren; Karen Jansen-West; Kim Malphrus; Simone Eggert; Hiroko Maruyama; Barbara A Cottrell; Pritam Das; Guriqbal S Basi; Edward H Koo; Todd E Golde
Journal:  J Biol Chem       Date:  2011-08-25       Impact factor: 5.157

2.  Loss of PAFAH1B2 reduces amyloid-β generation by promoting the degradation of amyloid precursor protein C-terminal fragments.

Authors:  Richard M Page; Anna Münch; Thomas Horn; Peer-Hendrik Kuhn; Alessio Colombo; Orly Reiner; Michael Boutros; Harald Steiner; Stefan F Lichtenthaler; Christian Haass
Journal:  J Neurosci       Date:  2012-12-12       Impact factor: 6.167

3.  Induced dimerization of the amyloid precursor protein leads to decreased amyloid-beta protein production.

Authors:  Simone Eggert; Brea Midthune; Barbara Cottrell; Edward H Koo
Journal:  J Biol Chem       Date:  2009-07-13       Impact factor: 5.157

Review 4.  Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer's Disease.

Authors:  Wioletta Rozpedek; Lukasz Markiewicz; J Alan Diehl; Dariusz Pytel; Ireneusz Majsterek
Journal:  Curr Med Chem       Date:  2015       Impact factor: 4.530

5.  Rapid and direct transport of cell surface APP to the lysosome defines a novel selective pathway.

Authors:  Angela Lorenzen; Jonathan Samosh; Kenneth Vandewark; Pieter H Anborgh; Claudia Seah; Ana C Magalhaes; Sean P Cregan; Stephen S G Ferguson; Stephen H Pasternak
Journal:  Mol Brain       Date:  2010-04-21       Impact factor: 4.041

6.  Cell-type-specific processing of the amyloid precursor protein by Presenilin during Drosophila development.

Authors:  Alexander Loewer; Peter Soba; Konrad Beyreuther; Renato Paro; Gunter Merdes
Journal:  EMBO Rep       Date:  2004-04       Impact factor: 8.807

7.  Alternative Selection of β-Site APP-Cleaving Enzyme 1 (BACE1) Cleavage Sites in Amyloid β-Protein Precursor (APP) Harboring Protective and Pathogenic Mutations within the Aβ Sequence.

Authors:  Ayano Kimura; Saori Hata; Toshiharu Suzuki
Journal:  J Biol Chem       Date:  2016-09-29       Impact factor: 5.157

8.  An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta production.

Authors:  Yuan Tian; Bhramdeo Bassit; Deming Chau; Yue-Ming Li
Journal:  Nat Struct Mol Biol       Date:  2010-01-10       Impact factor: 15.369

9.  Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate γ-Secretase Activities.

Authors:  Eugene Futai; Satoko Osawa; Tetsuo Cai; Tomoya Fujisawa; Shoichi Ishiura; Taisuke Tomita
Journal:  J Biol Chem       Date:  2015-11-11       Impact factor: 5.157

10.  Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Abeta42 reduces their differentiation potential.

Authors:  Markus Uhrig; Peter Brechlin; Olaf Jahn; Yuri Knyazev; Annette Weninger; Laura Busia; Kamran Honarnejad; Markus Otto; Tobias Hartmann
Journal:  BMC Med       Date:  2008-12-16       Impact factor: 8.775
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