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


ABSTRACT: 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 (A?) 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 A? 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 A? accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3? form (GSK3?-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.

SUBMITTER: Jeong J 

PROVIDER: S-EPMC7426148 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Jeong Jihoon J   Park Hyung Joon HJ   Mun Bo-Ram BR   Jang Ju Kyong JK   Choi Yong Moon YM   Choi Won-Seok WS  

PloS one 20200813 8


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  ...[more]

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