Cited 2 time in webofscience Cited 4 time in scopus

Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD

Title
Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD
Authors
Han, Kyung-MinKang, Ri JinJeon, HyongjunLee, Hyun-juLee, Ji-SooPark, HyunHeeJeon, Seong GakSuk, KyounghoSeo, JinsooHoe, Hyang-Sook
DGIST Authors
Seo, Jinsoo
Issue Date
2020-07
Citation
Cells, 9(7), 1665
Type
Article
Article Type
Article
Author Keywords
regorafenibneuroinflammationdendritic spineamyloid betatauaging
Keywords
AMYLOID-BETA PEPTIDEALZHEIMERSMICROGLIAPROTEINTAUNEUROBIOLOGYINVOLVEMENTPATHWAYSKINASEROLES
ISSN
2073-4409
Abstract
The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer's disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Regorafenib affected AKT signaling to attenuate lipopolysaccharide (LPS)-mediated expression of proinflammatory cytokines in BV2 microglial cells and primary cultured microglia and astrocytes. In addition, regorafenib suppressed LPS-induced neuroinflammatory responses in LPS-injected wild-type mice. In 5x FAD mice (a mouse model of AD), regorafenib ameliorated AD pathology, as evidenced by increased dendritic spine density and decreased Aβ plaque levels, by modulating APP processing and APP processing-associated proteins. Furthermore, regorafenib-injected 5x FAD mice displayed significantly reduced tau phosphorylation at T212 and S214 (AT100) due to the downregulation of glycogen synthase kinase-3 beta (GSK3β) activity. Taken together, our results indicate that regorafenib has beneficial effects on neuroinflammation, AD pathology, and dendritic spine formation in vitro and in vivo.
URI
http://hdl.handle.net/20.500.11750/12579
DOI
10.3390/cells9071655
Publisher
MDPI AG
Related Researcher
  • Author Seo, Jinsoo Laboratory of Aging Brain
  • Research Interests iPSC; Alzheimer's disease; Neurodegeneration; Synapse; Neuroscience
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Aging Brain1. Journal Articles


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