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Type: Journal article
Title: The development of an in vivo γ-secretase assay using zebrafish embryos
Other Titles: The development of an in vivo gamma-secretase assay using zebrafish embryos
Author: Wilson, L.
Lardelli, M.
Citation: Journal of Alzheimer's Disease, 2013; 36(3):521-534
Publisher: IOS Press
Issue Date: 2013
ISSN: 1387-2877
Statement of
Lachlan Wilson and Michael Lardelli
Abstract: Aberrant proteolytic processing of amyloid-β protein precursor by γ-secretase complexes may result in an imbalance between production and clearance of the Aβ proteolytic product and promote neuronal dysfunction and death. Presenilin proteins form the catalytic core of γ-secretase complexes. The zebrafish, Danio rerio, is a versatile vertebrate model for investigating the molecular basis of Alzheimer's disease pathology. It possesses genes orthologous to human PSEN1 and PSEN2 (psen1 and psen2 respectively), and AβPP (appa and appb that are duplicates of an ancestral AβPP orthologue). Currently there is no in vivo assay appropriate for directly monitoring γ-secretase activity. Here, we describe such an assay in which the level of a γ-secretase substrate (a modified form of Appa protein) is observed in zebrafish embryos by western immunoblotting relative to a co-expressed protein not subject to γ-secretase activity. We have used the assay to analyze the effects on γ-secretase activity of blocking translation of transcripts of zebrafish psen1 and/or psen2.
Keywords: Alzheimer's disease; amyloid-β protein precursor; assay; γ-secretase; morpholinos; presenilin; truncated protein; zebrafish
Rights: © 2013 – IOS Press and the authors. All rights reserved.
RMID: 0020130832
DOI: 10.3233/JAD-130332
Appears in Collections:Genetics publications

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