The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice

Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and mas...

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Bibliographic Details
Published in:Molecular brain 2020-09, Vol.13 (1), p.1-131, Article 131
Main Authors: Jeon, Seong Gak, Lee, Hyun-ju, Park, HyunHee, Han, Kyung-Min, Hoe, Hyang-Sook
Format: Article
Language:English
Subjects:
5xFAD mice
Advertising executives
Alzheimer's disease
Amyloid beta
Angiogenesis
Binding sites
Cancer therapies
Cognitive ability
Cyclin-dependent kinases
Dasatinib
Disease
Epidemiology
Immunohistochemistry
Kinases
Medical research
Micro Report
Nervous system diseases
Neurodegenerative diseases
Pathology
Permeability
Phosphorylation
Protein-tyrosine kinase
Senile plaques
Tau
Tau protein
Tyrosine
Vascular endothelial growth factor
Vascular endothelial growth factor receptors
Vatalanib
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Summary:Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and masitinib for AD, with reported beneficial effects in the AD brain. The TKI vatalanib inhibits angiogenesis by inhibiting vascular endothelial growth factor receptor (VEGFR). Although changes in VEGF and VEGFR have been documented in AD, the effect of vatalanib on AD pathology has not been investigated. In this study, the effects of vatalanib on tau phosphorylation and Aβ accumulation in 5xFAD mice, a model of AD, were evaluated by immunohistochemistry. Vatalanib administration significantly reduced tau phosphorylation at AT8 and AT100 by increasing p-GSK-3β (Ser9) in 5xFAD mice. In addition, vatalanib reduced the number and area of Aβ plaques in the cortex in 5xFAD mice. Our results suggest that vatalanib has potential as a regulator of AD pathology.
ISSN:1756-6606
1756-6606
DOI:10.1186/s13041-020-00673-7