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Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells
He, Xiaping1,2,3; Li, Zhenhui1,2; Rizak, Joshua D.1; Wu, Shihao1,2; Wang, Zhengbo1; He, Rongqiao4,5; Su, Min3; Qin, Dongdong1; Wang, Jingkun3; Hu, Xintian1,6,7; Dongdong Qin; Jingkun Wang; Xintian Hu
2017-01-31
发表期刊Frontiers in Neuroscience
通讯作者邮箱qindong108@163.com ; wjkyimm@163.com ; xthu@mail.kiz.ac.cn
ISSN1662-453X
文章类型Article
卷号10期号:0页码:598
摘要

Recent studies have demonstrated that formaldehyde (FA)-induced neurotoxicity is important in the pathogenesis of Alzheimer's disease (AD). Elevated levels of FA have been associated with memory impairments and the main hallmarks of AD pathology, including beta-amyloid plaques, tau protein hyperphosphorylation, and neuronal loss. Resveratrol (Res), as a polyphenol anti-oxidant, has been considered to have therapeutic potential for the treatment of AD. However, it has not been elucidated whether Res can exert its neuroprotective effects against FA-induced neuronal damages related to AD pathology. To answer this question, the effects of Res were investigated on Neuro-2a (N2a) cells prior to and after FA exposure. The experiments found that pre-treatment with Res significantly decreased FA-induced cytotoxicity, reduced cell apoptosis rates, and inhibited the hyperphosphorylation of tau protein at Thr181 in a dose-dependent manner. Further tests revealed that this effect was associated with the suppression of glycogen synthase kinase (GSK-3 beta) and calmodulin-dependent protein kinase II (CaMKII) activities, both of which are important kinases for tau protein hyperphosphorylation. In addition, Res was found to increase the activity of phosphoseryl/phosphothreonyl protein phosphatase-2A (PP2A). In summary, these findings provide evidence that Res protects N2a cells from FA-induced damages and suggests that inhibition of GSK-3 beta and CaMKII and the activation of PP2A by Res protect against the hyperphosphorylation and/or mediates the dephosphorylation of tau protein, respectively. These possible mechanisms underlying the neuroprotective effects of Res against FA-induced damages provide another perspective on AD treatment via inhibition of tau protein hyperhosphorylation.

关键词Alzheimer's disease formaldehyde resveratrol tau protein GSK-3 beta CaMKII PP2A
DOI10.3389/fnins.2016.00598
收录类别SCI
语种英语
项目资助者National Program for Key Basic Research Projects (973 Programs)(2015CB755605 ; Strategic Priority Research Program of the CAS(XDB02020005) ; Key Research Program of the Chinese Academy of Sciences ; Selected Frontier Scientific Significant Breakthrough Project of the CAS ; Key Program of the Chinese Academy of Sciences(KZCC-EW-103-2) ; Training Program of the Major Research Plan of the National Natural Science Foundation of China(91332120) ; National Natural Science Foundation of China(81471312 ; Yunnan Provincial Project to Attract One-hundred Exceptional Talents From Overseas ; Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(2014FA047) ; 2012CB825503 ; 31271167 ; 2012CBA01304) ; 81271495 ; 81460352)
WOS研究方向Neurosciences & Neurology
WOS类目Neurosciences
WOS记录号WOS:000392965900001
WOS标题词Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]ALZHEIMER-DISEASE BRAIN ; IN-VITRO ; AMYLOID-BETA ; PATHOLOGY ; KINASE ; MEMORY ; SITES ; DEPHOSPHORYLATION ; PHOSPHATASES ; AGGREGATION
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文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/21189
专题中国科学院心理健康重点实验室
通讯作者Dongdong Qin; Jingkun Wang; Xintian Hu
作者单位1.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Kunming, Peoples R China
2.Univ Chinese Acad Sci, Kunming Coll Life Sci, Nerve Syst Coding Discipline Grp, Kunming, Peoples R China
3.Yunnan Prov Co, Key Lab TCM & Ethn Drug New Drug Creat, Yunnan Inst Mat Med, Yunnan Bai Yao Grp,Innovat & R&D Ctr, Kunming, Peoples R China
4.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing, Peoples R China
5.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing, Peoples R China
6.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
7.Chinese Acad Sci, Kunming Primate Res Ctr, Kunming Inst Zool, Shanghai, Peoples R China
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He, Xiaping,Li, Zhenhui,Rizak, Joshua D.,et al. Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells[J]. Frontiers in Neuroscience,2017,10(0):598.
APA He, Xiaping.,Li, Zhenhui.,Rizak, Joshua D..,Wu, Shihao.,Wang, Zhengbo.,...&Xintian Hu.(2017).Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells.Frontiers in Neuroscience,10(0),598.
MLA He, Xiaping,et al."Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells".Frontiers in Neuroscience 10.0(2017):598.
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