The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice
Abstract 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 dasatini...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-020-00673-7 |
| _version_ | 1818037547575541760 |
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| author | Seong Gak Jeon Hyun-ju Lee HyunHee Park Kyung-Min Han Hyang-Sook Hoe |
| author_facet | Seong Gak Jeon Hyun-ju Lee HyunHee Park Kyung-Min Han Hyang-Sook Hoe |
| author_sort | Seong Gak Jeon |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T07:28:35Z |
| format | Article |
| id | doaj.art-6316625f6cac48cea72368ed7b9fa49f |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-10T07:28:35Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-6316625f6cac48cea72368ed7b9fa49f2022-12-22T01:57:39ZengBMCMolecular Brain1756-66062020-09-011311410.1186/s13041-020-00673-7The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD miceSeong Gak Jeon0Hyun-ju Lee1HyunHee Park2Kyung-Min Han3Hyang-Sook Hoe4Department of Neural Development and Disease, Korea Brain Research Institute (KBRI)Department of Neural Development and Disease, Korea Brain Research Institute (KBRI)Department of Neural Development and Disease, Korea Brain Research Institute (KBRI)Department of Neural Development and Disease, Korea Brain Research Institute (KBRI)Department of Neural Development and Disease, Korea Brain Research Institute (KBRI)Abstract 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.http://link.springer.com/article/10.1186/s13041-020-00673-7Alzheimer’s diseaseTauAmyloid beta5xFAD miceVatalanibVascular endothelial growth factor |
| spellingShingle | Seong Gak Jeon Hyun-ju Lee HyunHee Park Kyung-Min Han Hyang-Sook Hoe The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice Molecular Brain Alzheimer’s disease Tau Amyloid beta 5xFAD mice Vatalanib Vascular endothelial growth factor |
| title | The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice |
| title_full | The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice |
| title_fullStr | The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice |
| title_full_unstemmed | The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice |
| title_short | The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice |
| title_sort | vegf inhibitor vatalanib regulates ad pathology in 5xfad mice |
| topic | Alzheimer’s disease Tau Amyloid beta 5xFAD mice Vatalanib Vascular endothelial growth factor |
| url | http://link.springer.com/article/10.1186/s13041-020-00673-7 |
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