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

Autor: Criado-Marrero M; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Gebru NT; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Gould LA; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Blazier DM; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Vidal-Aguiar Y; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Smith TM; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Abdelmaboud SS; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Shelton LB; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Wang X; Department of Molecular Pharmacology and Physiology, College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Dahrendorff J; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Beaulieu-Abdelahad D; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Dickey CA; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA., Blair LJ; Department of Molecular Medicine, Morsani College of Medicine, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA. laurablair@usf.edu.; Research Service, James A Haley Veterans Hospital, Tampa, FL, USA. laurablair@usf.edu.
Jazyk: angličtina
Zdroj: NPJ aging and mechanisms of disease [NPJ Aging Mech Dis] 2021 May 03; Vol. 7 (1), pp. 9. Date of Electronic Publication: 2021 May 03.
DOI: 10.1038/s41514-021-00062-x
Abstrakt: 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.
Databáze: MEDLINE
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