14-3-3θ Does Not Protect against Behavioral or Pathological Deficits in Alzheimer's Disease Mouse Models.

Autor:	Gannon M; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294., Wang B; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294., Stringfellow SA; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294.; University of South Alabama College of Medicine, Mobile, AL 36688., Quintin S; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294.; Medical Scientist Training Program, University of Florida, Gainesville, FL 32611., Mendoza I; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294., Srikantha T; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294., Roberts AC; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294., Saito T; RIKEN Center for Brain Science, Saitama 351-0198, Japan.; Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduates School of Medical Sciences, Nagaya 467-8601, Japan., Saido TC; RIKEN Center for Brain Science, Saitama 351-0198, Japan., Roberson ED; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294., Yacoubian TA; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294 tyacoubian@uabmc.edu.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2022 Jun 24; Vol. 9 (3). Date of Electronic Publication: 2022 Jun 24 (Print Publication: 2022).
DOI:	10.1523/ENEURO.0368-21.2022
Abstrakt:	Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with synaptic dysfunction and dendritic spine loss and the pathologic hallmarks of β-amyloid (Aβ) plaques and hyperphosphorylated tau tangles. 14-3-3 proteins are a highly conserved family of proteins whose functions include regulation of protein folding, neuronal architecture, and synaptic function. Additionally, 14-3-3s interact with both Aβ and tau, and reduced levels of 14-3-3s have been shown in the brains of AD patients and in AD mouse models. Here, we examine the neuroprotective potential of the 14-3-3θ isoform in AD models. We demonstrate that 14-3-3θ overexpression is protective and 14-3-3θ inhibition is detrimental against oligomeric Aβ-induced neuronal death in primary cortical cultures. Overexpression of 14-3-3θ using an adeno-associated viral (AAV) vector failed to improve performance on behavioral tests, improve Aβ pathology, or affect synaptic density in the J20 AD mouse model. Similarly, crossing a second AD mouse model, the App NL-G-F knock-in (APP KI) mouse, with 14-3-3θ transgenic mice failed to rescue behavioral deficits, reduce Aβ pathology, or impact synaptic density in the APP KI mouse model. 14-3-3θ is likely partially insolubilized in the APP models, as demonstrated by proteinase K digestion. These findings do not support increasing 14-3-3θ expression as a therapeutic approach for AD. (Copyright © 2022 Gannon et al.)
Databáze:	MEDLINE
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