UM
Artemisinin improved neuronal functions in Alzheimer's disease animal model 3xtg mice and neuronal cells via stimulating the ERK/CREB signaling pathway
Zhao,Xia; Li,Shuai; Gaur,Uma; Zheng,Wenhua
2020
Source PublicationAging and Disease
Volume11Issue:4Pages:801-819
AbstractThe most common form of dementia is Alzheimer's disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer's disease is not known at present but toxicity of amyloid-beta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer's disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer's disease.
Keyword3×Tg mice Alzheimer's disease Amyloid beta Artemisinin Cognitive behavior SH-SY5Ycells
DOI10.14336/AD.2019.0813
URLView the original
Language英語English
Scopus ID2-s2.0-85090544641
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorZheng,Wenhua
AffiliationCenter of Reproduction,Development and Aging and Institute of Translation Medicine,Faculty of Health Sciences,University of Macau,Taipa,Macao
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
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Zhao,Xia,Li,Shuai,Gaur,Uma,et al. Artemisinin improved neuronal functions in Alzheimer's disease animal model 3xtg mice and neuronal cells via stimulating the ERK/CREB signaling pathway[J]. Aging and Disease,2020,11(4):801-819.
APA Zhao,Xia,Li,Shuai,Gaur,Uma,&Zheng,Wenhua.(2020).Artemisinin improved neuronal functions in Alzheimer's disease animal model 3xtg mice and neuronal cells via stimulating the ERK/CREB signaling pathway.Aging and Disease,11(4),801-819.
MLA Zhao,Xia,et al."Artemisinin improved neuronal functions in Alzheimer's disease animal model 3xtg mice and neuronal cells via stimulating the ERK/CREB signaling pathway".Aging and Disease 11.4(2020):801-819.
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