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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 β-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human tau with n...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223516/ https://www.ncbi.nlm.nih.gov/pubmed/35742871 http://dx.doi.org/10.3390/ijms23126427 |
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author | Ferrer, Isidro Andrés-Benito, Pol Ausín, Karina Cartas-Cejudo, Paz Lachén-Montes, Mercedes del Rio, José Antonio Fernández-Irigoyen, Joaquín Santamaría, Enrique |
author_facet | Ferrer, Isidro Andrés-Benito, Pol Ausín, Karina Cartas-Cejudo, Paz Lachén-Montes, Mercedes del Rio, José Antonio Fernández-Irigoyen, Joaquín Santamaría, Enrique |
author_sort | Ferrer, Isidro |
collection | PubMed |
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 β-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. |
format | Online Article Text |
id | pubmed-9223516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92235162022-06-24 Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model Ferrer, Isidro Andrés-Benito, Pol Ausín, Karina Cartas-Cejudo, Paz Lachén-Montes, Mercedes del Rio, José Antonio Fernández-Irigoyen, Joaquín Santamaría, Enrique Int J Mol Sci Article 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 β-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 2022-06-08 /pmc/articles/PMC9223516/ /pubmed/35742871 http://dx.doi.org/10.3390/ijms23126427 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ferrer, Isidro Andrés-Benito, Pol Ausín, Karina Cartas-Cejudo, Paz Lachén-Montes, Mercedes del Rio, José Antonio Fernández-Irigoyen, Joaquín Santamaría, Enrique 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 |
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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223516/ https://www.ncbi.nlm.nih.gov/pubmed/35742871 http://dx.doi.org/10.3390/ijms23126427 |
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