Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models

The most accepted hypothesis in Alzheimer's disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the conse...

Descripción completa

Detalles Bibliográficos
Autores: de la Cueva, Macarena, Antequera, Desireé, Ordóñez-Gutiérrez, Lara, Wandosell, Francisco, Camins, Antonio, Carro, Eva, Bartolome, Fernando
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15898
Acceso en línea:http://hdl.handle.net/20.500.12105/15898
Access Level:acceso abierto
Palabra clave:Alzheimer Disease
Amyloidosis
Amyloid
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Animals
Autophagy
Disease Models, Animal
Disease Progression
Mice
Mice, Transgenic
Mitochondrial Dynamics
Models, Theoretical
id ES_aa073efbadc7c148809b385aa6d7edbf
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/15898
network_acronym_str ES
network_name_str España
repository_id_str
spelling Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental modelsde la Cueva, MacarenaAntequera, DesireéOrdóñez-Gutiérrez, LaraWandosell, FranciscoCamins, AntonioCarro, EvaBartolome, FernandoAlzheimer DiseaseAmyloidosisAmyloidAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAutophagyDisease Models, AnimalDisease ProgressionMiceMice, TransgenicMitochondrial DynamicsModels, TheoreticalThe most accepted hypothesis in Alzheimer's disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the consequence of AD. It is however, clear that Aβ accumulation exerts toxic effects in the cerebral cells. It is important then to investigate all possible associated events that may help to design new therapeutic strategies to defeat or ameliorate the symptoms in AD. Alterations in the mitochondrial physiology have been found in AD but it is not still clear if they could be an early event in the disease progression associated to amyloidosis or other conditions. Using APP/PS1 mice, our results support published evidence and show imbalances in the mitochondrial dynamics in the cerebral cortex and hippocampus of these mice representing very early events in the disease progression. We demonstrate in cellular models that these imbalances are consequence of Aβ accumulation that ultimately induce increased mitophagy, a mechanism which selectively removes damaged mitochondria by autophagy. Along with increased mitophagy, we also found that Aβ independently increases autophagy in APP/PS1 mice. Therefore, mitochondrial dysfunction could be an early feature in AD, associated with amyloid overload.Nature Publishing GroupInstituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Comunidad de Madrid (España)Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)20232023-04-2620222022-06-1620222022-06-16research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/15898reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/158982026-06-12T12:43:37Z
dc.title.none.fl_str_mv Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
title Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
spellingShingle Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
de la Cueva, Macarena
Alzheimer Disease
Amyloidosis
Amyloid
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Animals
Autophagy
Disease Models, Animal
Disease Progression
Mice
Mice, Transgenic
Mitochondrial Dynamics
Models, Theoretical
title_short Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
title_full Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
title_fullStr Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
title_full_unstemmed Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
title_sort Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
dc.creator.none.fl_str_mv de la Cueva, Macarena
Antequera, Desireé
Ordóñez-Gutiérrez, Lara
Wandosell, Francisco
Camins, Antonio
Carro, Eva
Bartolome, Fernando
author de la Cueva, Macarena
author_facet de la Cueva, Macarena
Antequera, Desireé
Ordóñez-Gutiérrez, Lara
Wandosell, Francisco
Camins, Antonio
Carro, Eva
Bartolome, Fernando
author_role author
author2 Antequera, Desireé
Ordóñez-Gutiérrez, Lara
Wandosell, Francisco
Camins, Antonio
Carro, Eva
Bartolome, Fernando
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Comunidad de Madrid (España)
Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
dc.subject.none.fl_str_mv Alzheimer Disease
Amyloidosis
Amyloid
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Animals
Autophagy
Disease Models, Animal
Disease Progression
Mice
Mice, Transgenic
Mitochondrial Dynamics
Models, Theoretical
topic Alzheimer Disease
Amyloidosis
Amyloid
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Animals
Autophagy
Disease Models, Animal
Disease Progression
Mice
Mice, Transgenic
Mitochondrial Dynamics
Models, Theoretical
description The most accepted hypothesis in Alzheimer's disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the consequence of AD. It is however, clear that Aβ accumulation exerts toxic effects in the cerebral cells. It is important then to investigate all possible associated events that may help to design new therapeutic strategies to defeat or ameliorate the symptoms in AD. Alterations in the mitochondrial physiology have been found in AD but it is not still clear if they could be an early event in the disease progression associated to amyloidosis or other conditions. Using APP/PS1 mice, our results support published evidence and show imbalances in the mitochondrial dynamics in the cerebral cortex and hippocampus of these mice representing very early events in the disease progression. We demonstrate in cellular models that these imbalances are consequence of Aβ accumulation that ultimately induce increased mitophagy, a mechanism which selectively removes damaged mitochondria by autophagy. Along with increased mitophagy, we also found that Aβ independently increases autophagy in APP/PS1 mice. Therefore, mitochondrial dysfunction could be an early feature in AD, associated with amyloid overload.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-06-16
2022
2022-06-16
2023
2023-04-26
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/20.500.12105/15898
url http://hdl.handle.net/20.500.12105/15898
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
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
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
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416109113868288
score 15.811543

Similares en LA Referencia