Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2

Mutations in amyloid precursor protein (APP), and presenilin-1 and presenilin-2 (PS1 and PS2) have causally been implicated in Familial Alzheimer’s Disease (FAD), but the mechanistic link between the mutations and the early onset of neurodegeneration is still debated. Although no consensus has yet b...

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Autores: Kipanyula, Maulilio J., Wong, Andrea K.C., Fasolato, Cristina, Contreras Balsa, Laura, Zampese, Enrico, Lazzari, Cristian, Pizzo, Paola, Pozzan, Tullio
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/710906
Acceso en línea:http://hdl.handle.net/10486/710906
https://dx.doi.org/10.1111/j.1474-9726.2012.00858.x
Access Level:acceso abierto
Palabra clave:Alzheimer
Calcium
Endoplasmic reticulum
Mitochondria
Neurons
Presenilin
Biología y Biomedicina / Biología
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spelling Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2Kipanyula, Maulilio J.Wong, Andrea K.C.Fasolato, CristinaContreras Balsa, LauraZampese, EnricoLazzari, CristianPizzo, PaolaPozzan, TullioAlzheimerCalciumEndoplasmic reticulumMitochondriaNeuronsPresenilinBiología y Biomedicina / BiologíaMutations in amyloid precursor protein (APP), and presenilin-1 and presenilin-2 (PS1 and PS2) have causally been implicated in Familial Alzheimer’s Disease (FAD), but the mechanistic link between the mutations and the early onset of neurodegeneration is still debated. Although no consensus has yet been reached, most data suggest that both FAD-linked PS mutants and endogenous PSs are involved in cellular Ca2+ homeostasis. We here investigated subcellular Ca2+ handling in primary neuronal cultures and acute brain slices from wild type and transgenic mice carrying the FAD-linked PS2-N141I mutation, either alone or in the presence of the APP Swedish mutation. Compared with wild type, both types of transgenic neurons show a similar reduction in endoplasmic reticulum (ER) Ca2+ content and decreased response to metabotropic agonists, albeit increased Ca2+ release induced by caffeine. In both transgenic neurons, we also observed a higher ER–mitochondria juxtaposition that favors increased mitochondrial Ca2+ uptake upon ER Ca2+ release. A model is described that integrates into a unifying hypothesis the contradictory effects on Ca2+ homeostasis of different PS mutations and points to the relevance of these findings in neurodegeneration and agingThis work was supported by the Italian Ministry of University and Research (to C.F., P.P., and T.P.), the Veneto Region, the Italian Institute of Technology, the Strategic Projects of the University of Padua, the Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO) (to T.P.) and the University of Padua (CPDA109513 ⁄ 10 to P.P.). M.J.K. was supported by a Ph.D. fellowship from the CARIPARO Foundation. L.C. by a long-term EMBO fellowship and C.L. by a Ph.D. fellowship from the University of PaduaWiley Open AccessDepartamento de Biología MolecularFacultad de Ciencias20122012-10-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/710906https://dx.doi.org/10.1111/j.1474-9726.2012.00858.xreponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7109062026-06-23T12:46:27Z
dc.title.none.fl_str_mv Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
title Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
spellingShingle Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
Kipanyula, Maulilio J.
Alzheimer
Calcium
Endoplasmic reticulum
Mitochondria
Neurons
Presenilin
Biología y Biomedicina / Biología
title_short Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
title_full Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
title_fullStr Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
title_full_unstemmed Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
title_sort Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2
dc.creator.none.fl_str_mv Kipanyula, Maulilio J.
Wong, Andrea K.C.
Fasolato, Cristina
Contreras Balsa, Laura
Zampese, Enrico
Lazzari, Cristian
Pizzo, Paola
Pozzan, Tullio
author Kipanyula, Maulilio J.
author_facet Kipanyula, Maulilio J.
Wong, Andrea K.C.
Fasolato, Cristina
Contreras Balsa, Laura
Zampese, Enrico
Lazzari, Cristian
Pizzo, Paola
Pozzan, Tullio
author_role author
author2 Wong, Andrea K.C.
Fasolato, Cristina
Contreras Balsa, Laura
Zampese, Enrico
Lazzari, Cristian
Pizzo, Paola
Pozzan, Tullio
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Alzheimer
Calcium
Endoplasmic reticulum
Mitochondria
Neurons
Presenilin
Biología y Biomedicina / Biología
topic Alzheimer
Calcium
Endoplasmic reticulum
Mitochondria
Neurons
Presenilin
Biología y Biomedicina / Biología
description Mutations in amyloid precursor protein (APP), and presenilin-1 and presenilin-2 (PS1 and PS2) have causally been implicated in Familial Alzheimer’s Disease (FAD), but the mechanistic link between the mutations and the early onset of neurodegeneration is still debated. Although no consensus has yet been reached, most data suggest that both FAD-linked PS mutants and endogenous PSs are involved in cellular Ca2+ homeostasis. We here investigated subcellular Ca2+ handling in primary neuronal cultures and acute brain slices from wild type and transgenic mice carrying the FAD-linked PS2-N141I mutation, either alone or in the presence of the APP Swedish mutation. Compared with wild type, both types of transgenic neurons show a similar reduction in endoplasmic reticulum (ER) Ca2+ content and decreased response to metabotropic agonists, albeit increased Ca2+ release induced by caffeine. In both transgenic neurons, we also observed a higher ER–mitochondria juxtaposition that favors increased mitochondrial Ca2+ uptake upon ER Ca2+ release. A model is described that integrates into a unifying hypothesis the contradictory effects on Ca2+ homeostasis of different PS mutations and points to the relevance of these findings in neurodegeneration and aging
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-10-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/710906
https://dx.doi.org/10.1111/j.1474-9726.2012.00858.x
url http://hdl.handle.net/10486/710906
https://dx.doi.org/10.1111/j.1474-9726.2012.00858.x
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley Open Access
publisher.none.fl_str_mv Wiley Open Access
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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