Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity

The cholinergic enzyme acetylcholinesterase (AChE) and the catalytic component of the gamma-secretase complex, presenilin-1 (PS1), are known to interact. In this study, we investigate the consequences of AChE-PS1 interactions, particularly the influence of AChE in PS1 levels and gamma-secretase acti...

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Autores: Campanari ML, García-Ayllón MS, Belbin O, Galcerán J, Lleó A, SAEZ, J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p4821
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/4821
Access Level:acceso abierto
Palabra clave:Acetylcholinesterase
Alzheimer's disease
gamma-secretase
inhibitor
presenilin 1
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spelling Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase ActivityCampanari MLGarcía-Ayllón MSBelbin OGalcerán JLleó ASAEZ, J.AcetylcholinesteraseAlzheimer's diseasegamma-secretaseinhibitorpresenilin 1The cholinergic enzyme acetylcholinesterase (AChE) and the catalytic component of the gamma-secretase complex, presenilin-1 (PS1), are known to interact. In this study, we investigate the consequences of AChE-PS1 interactions, particularly the influence of AChE in PS1 levels and gamma-secretase activity. PS1 is able to co-immunoprecipitate all AChE variants (AChE-R and AChE-T) and molecular forms (tetramers and light subunits) present in the human brain. Overexpression of AChE-R or AChE-T, or their respective inactive mutants, all trigger an increase in PS1 protein levels. The AChE species capable of triggering the biggest increase in PS1 levels is a complex of AChE with the membrane anchoring subunit proline-rich membrane anchor (PRiMA), which restricts the localization of the resulting AChE tetramer to the outer plasma membrane. Incubation of cultured cells with soluble AChE demonstrates that AChE is able to increase PS1 at both the protein and transcript levels. However, the increase of PS1 caused by soluble AChE is accompanied by a decrease in gamma-secretase activity as shown by the reduction of the processing of the amyloid-beta protein precursor. This inhibitory effect of AChE on gamma-secretase activity was also demonstrated by directly assessing accumulation of CTF-A beta PP in cell-free membrane preparations incubated with AChE. Our data suggest that AChE may function as an inhibitor of gamma-secretase activity.SAGE PUBLICATIONS LTD2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/4821JOURNAL OF ALZHEIMERS DISEASEISSN: 13872877ISSNe: 18758908reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p48212026-06-11T12:45:17Z
dc.title.none.fl_str_mv Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
title Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
spellingShingle Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
Campanari ML
Acetylcholinesterase
Alzheimer's disease
gamma-secretase
inhibitor
presenilin 1
title_short Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
title_full Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
title_fullStr Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
title_full_unstemmed Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
title_sort Acetylcholinesterase Modulates Presenilin-1 Levels and gamma-Secretase Activity
dc.creator.none.fl_str_mv Campanari ML
García-Ayllón MS
Belbin O
Galcerán J
Lleó A
SAEZ, J.
author Campanari ML
author_facet Campanari ML
García-Ayllón MS
Belbin O
Galcerán J
Lleó A
SAEZ, J.
author_role author
author2 García-Ayllón MS
Belbin O
Galcerán J
Lleó A
SAEZ, J.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Acetylcholinesterase
Alzheimer's disease
gamma-secretase
inhibitor
presenilin 1
topic Acetylcholinesterase
Alzheimer's disease
gamma-secretase
inhibitor
presenilin 1
description The cholinergic enzyme acetylcholinesterase (AChE) and the catalytic component of the gamma-secretase complex, presenilin-1 (PS1), are known to interact. In this study, we investigate the consequences of AChE-PS1 interactions, particularly the influence of AChE in PS1 levels and gamma-secretase activity. PS1 is able to co-immunoprecipitate all AChE variants (AChE-R and AChE-T) and molecular forms (tetramers and light subunits) present in the human brain. Overexpression of AChE-R or AChE-T, or their respective inactive mutants, all trigger an increase in PS1 protein levels. The AChE species capable of triggering the biggest increase in PS1 levels is a complex of AChE with the membrane anchoring subunit proline-rich membrane anchor (PRiMA), which restricts the localization of the resulting AChE tetramer to the outer plasma membrane. Incubation of cultured cells with soluble AChE demonstrates that AChE is able to increase PS1 at both the protein and transcript levels. However, the increase of PS1 caused by soluble AChE is accompanied by a decrease in gamma-secretase activity as shown by the reduction of the processing of the amyloid-beta protein precursor. This inhibitory effect of AChE on gamma-secretase activity was also demonstrated by directly assessing accumulation of CTF-A beta PP in cell-free membrane preparations incubated with AChE. Our data suggest that AChE may function as an inhibitor of gamma-secretase activity.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/4821
url https://fisabio.portalinvestigacion.com/publicaciones/4821
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SAGE PUBLICATIONS LTD
publisher.none.fl_str_mv SAGE PUBLICATIONS LTD
dc.source.none.fl_str_mv JOURNAL OF ALZHEIMERS DISEASE
ISSN: 13872877
ISSNe: 18758908
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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