The development of an in vivo γ-secretase assay using zebrafish embryos

Simple item page
dc.contributor.authorWilson, L.
dc.contributor.authorLardelli, M.
dc.date.issued2013
dc.description.abstractAberrant 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.
dc.description.statementofresponsibilityLachlan Wilson and Michael Lardelli
dc.identifier.citationJournal of Alzheimer's Disease, 2013; 36(3):521-534
dc.identifier.doi10.3233/JAD-130332
dc.identifier.issn1387-2877
dc.identifier.issn1875-8908
dc.identifier.orcidLardelli, M. [0000-0002-4289-444X]
dc.identifier.urihttp://hdl.handle.net/2440/80131
dc.language.isoen
dc.publisherIOS Press
dc.rights© 2013 – IOS Press and the authors. All rights reserved.
dc.source.urihttps://doi.org/10.3233/jad-130332
dc.subjectAlzheimer's disease
dc.subjectamyloid-β protein precursor
dc.subjectassay
dc.subjectγ-secretase
dc.subjectmorpholinos
dc.subjectpresenilin
dc.subjecttruncated protein
dc.subjectzebrafish
dc.titleThe development of an in vivo γ-secretase assay using zebrafish embryos
dc.title.alternativeThe development of an in vivo gamma-secretase assay using zebrafish embryos
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Genetics publications