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JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aβ) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology ha...

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Autores principales: Jeong, Jihoon, Park, Hyung Joon, Mun, Bo-Ram, Jang, Ju Kyong, Choi, Yong Moon, Choi, Won-Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426148/
https://www.ncbi.nlm.nih.gov/pubmed/32791516
http://dx.doi.org/10.1371/journal.pone.0237153
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author Jeong, Jihoon
Park, Hyung Joon
Mun, Bo-Ram
Jang, Ju Kyong
Choi, Yong Moon
Choi, Won-Seok
author_facet Jeong, Jihoon
Park, Hyung Joon
Mun, Bo-Ram
Jang, Ju Kyong
Choi, Yong Moon
Choi, Won-Seok
author_sort Jeong, Jihoon
collection PubMed
description Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aβ) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology has not yet been fully elucidated; thus, no drug that cures the disease has been approved. JBPOS0101 is a phenyl carbamate compound that has been tested as a drug for epileptic diseases. In our previous study, we showed that JBPOS0101 attenuated the accumulation of Aβ as well as the deficits in learning and memory in the 5xFAD mouse model. Here, we tested the dose effect (70 or 35 mg/kg) of JBPOS0101 on the memory defect and pathological markers and further investigated the underlying mechanisms in 5xFAD mice. In the behavior tests, JBPOS0101 treatment ameliorated deficits in learning and memory. Moreover, JBPOS0101 attenuated Aβ accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3β form (GSK3β-y216) in 5xFAD, which are responsible for tau phosphorylation, decreased in the JBPOS0101-treated groups. Furthermore, the elevation of reactive astrocytes and microglia in 5xFAD mice was attenuated in JBPOS0101-treated groups. These data suggest that JBPOS0101 may be a new drug candidate to lessen amyloid- and tau-related pathology by regulating glial cells.
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spelling pubmed-74261482020-08-20 JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model Jeong, Jihoon Park, Hyung Joon Mun, Bo-Ram Jang, Ju Kyong Choi, Yong Moon Choi, Won-Seok PLoS One Research Article Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aβ) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology has not yet been fully elucidated; thus, no drug that cures the disease has been approved. JBPOS0101 is a phenyl carbamate compound that has been tested as a drug for epileptic diseases. In our previous study, we showed that JBPOS0101 attenuated the accumulation of Aβ as well as the deficits in learning and memory in the 5xFAD mouse model. Here, we tested the dose effect (70 or 35 mg/kg) of JBPOS0101 on the memory defect and pathological markers and further investigated the underlying mechanisms in 5xFAD mice. In the behavior tests, JBPOS0101 treatment ameliorated deficits in learning and memory. Moreover, JBPOS0101 attenuated Aβ accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3β form (GSK3β-y216) in 5xFAD, which are responsible for tau phosphorylation, decreased in the JBPOS0101-treated groups. Furthermore, the elevation of reactive astrocytes and microglia in 5xFAD mice was attenuated in JBPOS0101-treated groups. These data suggest that JBPOS0101 may be a new drug candidate to lessen amyloid- and tau-related pathology by regulating glial cells. Public Library of Science 2020-08-13 /pmc/articles/PMC7426148/ /pubmed/32791516 http://dx.doi.org/10.1371/journal.pone.0237153 Text en © 2020 Jeong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jeong, Jihoon
Park, Hyung Joon
Mun, Bo-Ram
Jang, Ju Kyong
Choi, Yong Moon
Choi, Won-Seok
JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model
title JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model
title_full JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model
title_fullStr JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model
title_full_unstemmed JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model
title_short JBPOS0101 regulates amyloid beta, tau, and glial cells in an Alzheimer’s disease model
title_sort jbpos0101 regulates amyloid beta, tau, and glial cells in an alzheimer’s disease model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426148/
https://www.ncbi.nlm.nih.gov/pubmed/32791516
http://dx.doi.org/10.1371/journal.pone.0237153
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