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FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model
Abnormal accumulation of hyperphosphorylated tau induces pathogenesis in neurodegenerative diseases, like Alzheimer’s disease. Molecular chaperones with peptidyl-prolyl cis/trans isomerase (PPIase) activity are known to regulate these processes. Previously, in vitro studies have shown that the 52 kD...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093247/ https://www.ncbi.nlm.nih.gov/pubmed/33941782 http://dx.doi.org/10.1038/s41514-021-00062-x |
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author | Criado-Marrero, Marangelie Gebru, Niat T. Gould, Lauren A. Blazier, Danielle M. Vidal-Aguiar, Yamile Smith, Taylor M. Abdelmaboud, Salma S. Shelton, Lindsey B. Wang, Xinming Dahrendorff, Jan Beaulieu-Abdelahad, David Dickey, Chad A. Blair, Laura J. |
author_facet | Criado-Marrero, Marangelie Gebru, Niat T. Gould, Lauren A. Blazier, Danielle M. Vidal-Aguiar, Yamile Smith, Taylor M. Abdelmaboud, Salma S. Shelton, Lindsey B. Wang, Xinming Dahrendorff, Jan Beaulieu-Abdelahad, David Dickey, Chad A. Blair, Laura J. |
author_sort | Criado-Marrero, Marangelie |
collection | PubMed |
description | Abnormal accumulation of hyperphosphorylated tau induces pathogenesis in neurodegenerative diseases, like Alzheimer’s disease. Molecular chaperones with peptidyl-prolyl cis/trans isomerase (PPIase) activity are known to regulate these processes. Previously, in vitro studies have shown that the 52 kDa FK506-binding protein (FKBP52) interacts with tau inducing its oligomerization and fibril formation to promote toxicity. Thus, we hypothesized that increased expression of FKBP52 in the brains of tau transgenic mice would alter tau phosphorylation and neurofibrillary tangle formation ultimately leading to memory impairments. To test this, tau transgenic (rTg4510) and wild-type mice received bilateral hippocampal injections of virus overexpressing FKBP52 or GFP control. We examined hippocampal-dependent memory, synaptic plasticity, tau phosphorylation status, and neuronal health. This work revealed that rTg4510 mice overexpressing FKBP52 had impaired spatial learning, accompanied by long-term potentiation deficits and hippocampal neuronal loss, which was associated with a modest increase in total caspase 12. Together with previous studies, our findings suggest that FKBP52 may sensitize neurons to tau-mediated dysfunction via activation of a caspase-dependent pathway, contributing to memory and learning impairments. |
format | Online Article Text |
id | pubmed-8093247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80932472021-05-05 FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model Criado-Marrero, Marangelie Gebru, Niat T. Gould, Lauren A. Blazier, Danielle M. Vidal-Aguiar, Yamile Smith, Taylor M. Abdelmaboud, Salma S. Shelton, Lindsey B. Wang, Xinming Dahrendorff, Jan Beaulieu-Abdelahad, David Dickey, Chad A. Blair, Laura J. NPJ Aging Mech Dis Article Abnormal accumulation of hyperphosphorylated tau induces pathogenesis in neurodegenerative diseases, like Alzheimer’s disease. Molecular chaperones with peptidyl-prolyl cis/trans isomerase (PPIase) activity are known to regulate these processes. Previously, in vitro studies have shown that the 52 kDa FK506-binding protein (FKBP52) interacts with tau inducing its oligomerization and fibril formation to promote toxicity. Thus, we hypothesized that increased expression of FKBP52 in the brains of tau transgenic mice would alter tau phosphorylation and neurofibrillary tangle formation ultimately leading to memory impairments. To test this, tau transgenic (rTg4510) and wild-type mice received bilateral hippocampal injections of virus overexpressing FKBP52 or GFP control. We examined hippocampal-dependent memory, synaptic plasticity, tau phosphorylation status, and neuronal health. This work revealed that rTg4510 mice overexpressing FKBP52 had impaired spatial learning, accompanied by long-term potentiation deficits and hippocampal neuronal loss, which was associated with a modest increase in total caspase 12. Together with previous studies, our findings suggest that FKBP52 may sensitize neurons to tau-mediated dysfunction via activation of a caspase-dependent pathway, contributing to memory and learning impairments. Nature Publishing Group UK 2021-05-03 /pmc/articles/PMC8093247/ /pubmed/33941782 http://dx.doi.org/10.1038/s41514-021-00062-x Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Criado-Marrero, Marangelie Gebru, Niat T. Gould, Lauren A. Blazier, Danielle M. Vidal-Aguiar, Yamile Smith, Taylor M. Abdelmaboud, Salma S. Shelton, Lindsey B. Wang, Xinming Dahrendorff, Jan Beaulieu-Abdelahad, David Dickey, Chad A. Blair, Laura J. FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
title | FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
title_full | FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
title_fullStr | FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
title_full_unstemmed | FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
title_short | FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
title_sort | fkbp52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093247/ https://www.ncbi.nlm.nih.gov/pubmed/33941782 http://dx.doi.org/10.1038/s41514-021-00062-x |
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