Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.

The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric...

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Autores: Ettcheto Arriola, Miren, Sánchez-López, E. (Elena), Pons, Laura, Busquets Figueras, Oriol, Olloquequi, Jordi, Beas Zárate, Carlos, Pallàs i Llibería, Mercè, 1964-, García López, María Luisa, Auladell i Costa, M. Carme, Folch, Jaume, Camins Espuny, Antoni
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/118847
Acesso em linha:https://hdl.handle.net/2445/118847
Access Level:acceso abierto
Palavra-chave:Malaltia d'Alzheimer
Hipocamp (Cervell)
Receptors d'insulina
Mitocondris
Medicaments
Alzheimer's disease
Hippocampus (Brain)
Insulin receptors
Mitochondria
Drugs
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network_name_str España
repository_id_str
spelling Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.Ettcheto Arriola, MirenSánchez-López, E. (Elena)Pons, LauraBusquets Figueras, OriolOlloquequi, JordiBeas Zárate, CarlosPallàs i Llibería, Mercè, 1964-García López, María LuisaAuladell i Costa, M. CarmeFolch, JaumeCamins Espuny, AntoniMalaltia d'AlzheimerHipocamp (Cervell)Receptors d'insulinaMitocondrisMedicamentsAlzheimer's diseaseHippocampus (Brain)Insulin receptorsMitochondriaDrugsThe aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks.Elsevier B.V.2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/118847Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.redox.2017.06.003Redox Biology, 2017, vol. 13, p. 345 -352https://doi.org/10.1016/j.redox.2017.06.003cc-by-nc-nd (c) Elsevier B.V., 2017http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1188472026-05-27T06:46:51Z
dc.title.none.fl_str_mv Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
title Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
spellingShingle Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
Ettcheto Arriola, Miren
Malaltia d'Alzheimer
Hipocamp (Cervell)
Receptors d'insulina
Mitocondris
Medicaments
Alzheimer's disease
Hippocampus (Brain)
Insulin receptors
Mitochondria
Drugs
title_short Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
title_full Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
title_fullStr Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
title_full_unstemmed Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
title_sort Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways.
dc.creator.none.fl_str_mv Ettcheto Arriola, Miren
Sánchez-López, E. (Elena)
Pons, Laura
Busquets Figueras, Oriol
Olloquequi, Jordi
Beas Zárate, Carlos
Pallàs i Llibería, Mercè, 1964-
García López, María Luisa
Auladell i Costa, M. Carme
Folch, Jaume
Camins Espuny, Antoni
author Ettcheto Arriola, Miren
author_facet Ettcheto Arriola, Miren
Sánchez-López, E. (Elena)
Pons, Laura
Busquets Figueras, Oriol
Olloquequi, Jordi
Beas Zárate, Carlos
Pallàs i Llibería, Mercè, 1964-
García López, María Luisa
Auladell i Costa, M. Carme
Folch, Jaume
Camins Espuny, Antoni
author_role author
author2 Sánchez-López, E. (Elena)
Pons, Laura
Busquets Figueras, Oriol
Olloquequi, Jordi
Beas Zárate, Carlos
Pallàs i Llibería, Mercè, 1964-
García López, María Luisa
Auladell i Costa, M. Carme
Folch, Jaume
Camins Espuny, Antoni
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Hipocamp (Cervell)
Receptors d'insulina
Mitocondris
Medicaments
Alzheimer's disease
Hippocampus (Brain)
Insulin receptors
Mitochondria
Drugs
topic Malaltia d'Alzheimer
Hipocamp (Cervell)
Receptors d'insulina
Mitocondris
Medicaments
Alzheimer's disease
Hippocampus (Brain)
Insulin receptors
Mitochondria
Drugs
description The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/118847
url https://hdl.handle.net/2445/118847
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.redox.2017.06.003
Redox Biology, 2017, vol. 13, p. 345 -352
https://doi.org/10.1016/j.redox.2017.06.003
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier B.V., 2017
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier B.V., 2017
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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