Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model

Altered protein phosphorylation is a major pathologic modification in tauopathies and Alzheimer's disease (AD) linked to abnormal tau fibrillar deposits in neurofibrillary tangles (NFTs) and pre-tangles and beta-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human ta...

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Autores: Ferrer, Isidro (Ferrer Abizanda), Andrés Benito, Pol, Ausín, Karina, Cartas Cejudo, Paz, Lachén Montes, Mercedes, Rio, José Antonio del, Fernández Irigoyen, Joaquín, Santamaría, Enrique
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/187446
Acesso em linha:https://hdl.handle.net/2445/187446
Access Level:Acceso aberto
Palavra-chave:Malaltia d'Alzheimer
Proteïnes
Alzheimer's disease
Proteins
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spelling Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse ModelFerrer, Isidro (Ferrer Abizanda)Andrés Benito, PolAusín, KarinaCartas Cejudo, PazLachén Montes, MercedesRio, José Antonio delFernández Irigoyen, JoaquínSantamaría, EnriqueMalaltia d'AlzheimerProteïnesAlzheimer's diseaseProteinsAltered protein phosphorylation is a major pathologic modification in tauopathies and Alzheimer's disease (AD) linked to abnormal tau fibrillar deposits in neurofibrillary tangles (NFTs) and pre-tangles and beta-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human tau with no mutations in a murine knock-out background, show increased tau deposition in neurons but not NFTs and pre-tangles at the age of nine months. Label-free (phospho)proteomics and SWATH-MS identified 2065 proteins in hTau and wild-type (WT) mice. Only six proteins showed increased levels in hTau; no proteins were down-regulated. Increased tau phosphorylation in hTau was detected at Ser199, Ser202, Ser214, Ser396, Ser400, Thr403, Ser404, Ser413, Ser416, Ser422, Ser491, and Ser494, in addition to Thr181, Thr231, Ser396/Ser404, but not at Ser202/Thr205. In addition, 4578 phosphopeptides (corresponding to 1622 phosphoproteins) were identified in hTau and WT mice; 64 proteins were differentially phosphorylated in hTau. Sixty proteins were grouped into components of membranes, membrane signaling, synapses, vesicles, cytoskeleton, DNA/RNA/protein metabolism, ubiquitin/proteasome system, cholesterol and lipid metabolism, and cell signaling. These results showed that over-expression of human tau without pre-tangle and NFT formation preferentially triggers an imbalance in the phosphorylation profile of specific proteins involved in the cytoskeletal-membrane-signaling axis.MDPI AG2022202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/187446Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms23126427International Journal of Molecular Sciences, 2022, vol. 23, num. 12https://doi.org/10.3390/ijms23126427cc by (c) Ferrer, Isidro (Ferrer Abizanda) et al, 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1874462026-05-29T05:05:01Z
dc.title.none.fl_str_mv Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
title Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
spellingShingle Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
Ferrer, Isidro (Ferrer Abizanda)
Malaltia d'Alzheimer
Proteïnes
Alzheimer's disease
Proteins
title_short Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
title_full Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
title_fullStr Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
title_full_unstemmed Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
title_sort Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
dc.creator.none.fl_str_mv Ferrer, Isidro (Ferrer Abizanda)
Andrés Benito, Pol
Ausín, Karina
Cartas Cejudo, Paz
Lachén Montes, Mercedes
Rio, José Antonio del
Fernández Irigoyen, Joaquín
Santamaría, Enrique
author Ferrer, Isidro (Ferrer Abizanda)
author_facet Ferrer, Isidro (Ferrer Abizanda)
Andrés Benito, Pol
Ausín, Karina
Cartas Cejudo, Paz
Lachén Montes, Mercedes
Rio, José Antonio del
Fernández Irigoyen, Joaquín
Santamaría, Enrique
author_role author
author2 Andrés Benito, Pol
Ausín, Karina
Cartas Cejudo, Paz
Lachén Montes, Mercedes
Rio, José Antonio del
Fernández Irigoyen, Joaquín
Santamaría, Enrique
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Proteïnes
Alzheimer's disease
Proteins
topic Malaltia d'Alzheimer
Proteïnes
Alzheimer's disease
Proteins
description Altered protein phosphorylation is a major pathologic modification in tauopathies and Alzheimer's disease (AD) linked to abnormal tau fibrillar deposits in neurofibrillary tangles (NFTs) and pre-tangles and beta-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human tau with no mutations in a murine knock-out background, show increased tau deposition in neurons but not NFTs and pre-tangles at the age of nine months. Label-free (phospho)proteomics and SWATH-MS identified 2065 proteins in hTau and wild-type (WT) mice. Only six proteins showed increased levels in hTau; no proteins were down-regulated. Increased tau phosphorylation in hTau was detected at Ser199, Ser202, Ser214, Ser396, Ser400, Thr403, Ser404, Ser413, Ser416, Ser422, Ser491, and Ser494, in addition to Thr181, Thr231, Ser396/Ser404, but not at Ser202/Thr205. In addition, 4578 phosphopeptides (corresponding to 1622 phosphoproteins) were identified in hTau and WT mice; 64 proteins were differentially phosphorylated in hTau. Sixty proteins were grouped into components of membranes, membrane signaling, synapses, vesicles, cytoskeleton, DNA/RNA/protein metabolism, ubiquitin/proteasome system, cholesterol and lipid metabolism, and cell signaling. These results showed that over-expression of human tau without pre-tangle and NFT formation preferentially triggers an imbalance in the phosphorylation profile of specific proteins involved in the cytoskeletal-membrane-signaling axis.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
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://hdl.handle.net/2445/187446
url https://hdl.handle.net/2445/187446
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/10.3390/ijms23126427
International Journal of Molecular Sciences, 2022, vol. 23, num. 12
https://doi.org/10.3390/ijms23126427
dc.rights.none.fl_str_mv cc by (c) Ferrer, Isidro (Ferrer Abizanda) et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Ferrer, Isidro (Ferrer Abizanda) et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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