Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathologica...

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Autores: Rodriguez-Rodriguez, Patricia, Sandebring-Matton, Anna, Merino-Serrais, Paula, Parrado-Fernandez, Cristina, Rabano, Alberto, Winblad, Bengt, Avila, Jesús, Ferrer, Isidro (Ferrer Abizanda), Cedazo-Mínguez, Ángel
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/140347
Acceso en línea:https://hdl.handle.net/2445/140347
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Metabolisme
Cervell
Neurones
Resistència a la insulina
Alzheimer's disease
Metabolism
Brain
Neurons
Insulin resistance
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spelling Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neuronsRodriguez-Rodriguez, PatriciaSandebring-Matton, AnnaMerino-Serrais, PaulaParrado-Fernandez, CristinaRabano, AlbertoWinblad, BengtAvila, JesúsFerrer, Isidro (Ferrer Abizanda)Cedazo-Mínguez, ÁngelMalaltia d'AlzheimerMetabolismeCervellNeuronesResistència a la insulinaAlzheimer's diseaseMetabolismBrainNeuronsInsulin resistanceInsulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications.Oxford University Press2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/140347Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1093/brain/awx256Brain, 2017, vol. 40, num. 12, p. 3269-3285https://doi.org/10.1093/brain/awx256(c) Rodriguez-Rodriguez, Patricia et al., 2017info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1403472026-05-27T06:46:51Z
dc.title.none.fl_str_mv Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
title Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
spellingShingle Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
Rodriguez-Rodriguez, Patricia
Malaltia d'Alzheimer
Metabolisme
Cervell
Neurones
Resistència a la insulina
Alzheimer's disease
Metabolism
Brain
Neurons
Insulin resistance
title_short Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
title_full Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
title_fullStr Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
title_full_unstemmed Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
title_sort Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
dc.creator.none.fl_str_mv Rodriguez-Rodriguez, Patricia
Sandebring-Matton, Anna
Merino-Serrais, Paula
Parrado-Fernandez, Cristina
Rabano, Alberto
Winblad, Bengt
Avila, Jesús
Ferrer, Isidro (Ferrer Abizanda)
Cedazo-Mínguez, Ángel
author Rodriguez-Rodriguez, Patricia
author_facet Rodriguez-Rodriguez, Patricia
Sandebring-Matton, Anna
Merino-Serrais, Paula
Parrado-Fernandez, Cristina
Rabano, Alberto
Winblad, Bengt
Avila, Jesús
Ferrer, Isidro (Ferrer Abizanda)
Cedazo-Mínguez, Ángel
author_role author
author2 Sandebring-Matton, Anna
Merino-Serrais, Paula
Parrado-Fernandez, Cristina
Rabano, Alberto
Winblad, Bengt
Avila, Jesús
Ferrer, Isidro (Ferrer Abizanda)
Cedazo-Mínguez, Ángel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Metabolisme
Cervell
Neurones
Resistència a la insulina
Alzheimer's disease
Metabolism
Brain
Neurons
Insulin resistance
topic Malaltia d'Alzheimer
Metabolisme
Cervell
Neurones
Resistència a la insulina
Alzheimer's disease
Metabolism
Brain
Neurons
Insulin resistance
description Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications.
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/2445/140347
url https://hdl.handle.net/2445/140347
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1093/brain/awx256
Brain, 2017, vol. 40, num. 12, p. 3269-3285
https://doi.org/10.1093/brain/awx256
dc.rights.none.fl_str_mv (c) Rodriguez-Rodriguez, Patricia et al., 2017
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Rodriguez-Rodriguez, Patricia et al., 2017
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
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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