FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model

Abstract 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...

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Autores principales:	Marangelie Criado-Marrero, Niat T. Gebru, Lauren A. Gould, Danielle M. Blazier, Yamile Vidal-Aguiar, Taylor M. Smith, Salma S. Abdelmaboud, Lindsey B. Shelton, Xinming Wang, Jan Dahrendorff, David Beaulieu-Abdelahad, Chad A. Dickey, Laura J. Blair
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/b06d2c045077424ca482d80168b5726e
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spelling	oai:doaj.org-article:b06d2c045077424ca482d80168b5726e2021-12-02T15:37:57ZFKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model10.1038/s41514-021-00062-x2056-3973https://doaj.org/article/b06d2c045077424ca482d80168b5726e2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00062-xhttps://doaj.org/toc/2056-3973Abstract 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.Marangelie Criado-MarreroNiat T. GebruLauren A. GouldDanielle M. BlazierYamile Vidal-AguiarTaylor M. SmithSalma S. AbdelmaboudLindsey B. SheltonXinming WangJan DahrendorffDavid Beaulieu-AbdelahadChad A. DickeyLaura J. BlairNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Marangelie Criado-Marrero Niat T. Gebru Lauren A. Gould Danielle M. Blazier Yamile Vidal-Aguiar Taylor M. Smith Salma S. Abdelmaboud Lindsey B. Shelton Xinming Wang Jan Dahrendorff David Beaulieu-Abdelahad Chad A. Dickey Laura J. Blair FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model
description	Abstract 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	article
author	Marangelie Criado-Marrero Niat T. Gebru Lauren A. Gould Danielle M. Blazier Yamile Vidal-Aguiar Taylor M. Smith Salma S. Abdelmaboud Lindsey B. Shelton Xinming Wang Jan Dahrendorff David Beaulieu-Abdelahad Chad A. Dickey Laura J. Blair
author_facet	Marangelie Criado-Marrero Niat T. Gebru Lauren A. Gould Danielle M. Blazier Yamile Vidal-Aguiar Taylor M. Smith Salma S. Abdelmaboud Lindsey B. Shelton Xinming Wang Jan Dahrendorff David Beaulieu-Abdelahad Chad A. Dickey Laura J. Blair
author_sort	Marangelie Criado-Marrero
title	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_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_sort	fkbp52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b06d2c045077424ca482d80168b5726e
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FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model

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