Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain.

Autor: Rodriguez Ospina S; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Blazier DM; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Criado-Marrero M; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Gould LA; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Gebru NT; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Beaulieu-Abdelahad D; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Wang X; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, USA., Remily-Wood E; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Chaput D; Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA., Stevens S; Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA., Uversky VN; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.; Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutskiy Pereulok, 9, 141700 Dolgoprudny, Russia., Bickford PC; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, USA.; Research Service, James A. Haley Veterans' Hospital, Tampa, FL 33620, USA.; Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL 33613, USA., Dickey CA; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA., Blair LJ; USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL 33613, USA.; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.; Research Service, James A. Haley Veterans' Hospital, Tampa, FL 33620, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jan 13; Vol. 23 (2). Date of Electronic Publication: 2022 Jan 13.
DOI: 10.3390/ijms23020851
Abstrakt: The microtubule-associated protein tau pathologically accumulates and aggregates in Alzheimer's disease (AD) and other tauopathies, leading to cognitive dysfunction and neuronal loss. Molecular chaperones, like small heat-shock proteins (sHsps), can help deter the accumulation of misfolded proteins, such as tau. Here, we tested the hypothesis that the overexpression of wild-type Hsp22 (wtHsp22) and its phosphomimetic (S24,57D) Hsp22 mutant (mtHsp22) could slow tau accumulation and preserve memory in a murine model of tauopathy, rTg4510. Our results show that Hsp22 protected against deficits in synaptic plasticity and cognition in the tauopathic brain. However, we did not detect a significant change in tau phosphorylation or levels in these mice. This led us to hypothesize that the functional benefit was realized through the restoration of dysfunctional pathways in hippocampi of tau transgenic mice since no significant benefit was measured in non-transgenic mice expressing wtHsp22 or mtHsp22. To identify these pathways, we performed mass spectrometry of tissue lysates from the injection site. Overall, our data reveal that Hsp22 overexpression in neurons promotes synaptic plasticity by regulating canonical pathways and upstream regulators that have been characterized as potential AD markers and synaptogenesis regulators, like EIF4E and NFKBIA.
Databáze: MEDLINE
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