Institutional Repository of Key Laboratory of Mental Health, CAS
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 | |
通讯作者邮箱 | qindong108@163.com ; wjkyimm@163.com ; xthu@mail.kiz.ac.cn |
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 |
2017-01-31 | |
语种 | 英语 |
DOI | 10.3389/fnins.2016.00598 |
发表期刊 | Frontiers in Neuroscience |
ISSN | 1662-453X |
卷号 | 10期号:0页码:598 |
期刊论文类型 | Article |
收录类别 | SCI |
WOS关键词 | ALZHEIMER-DISEASE BRAIN ; IN-VITRO ; AMYLOID-BETA ; PATHOLOGY ; KINASE ; MEMORY ; SITES ; DEPHOSPHORYLATION ; PHOSPHATASES ; AGGREGATION |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
WOS研究方向 | Neurosciences & Neurology |
WOS类目 | Neurosciences |
WOS记录号 | WOS:000392965900001 |
资助机构 | 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 ; Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(2014FA047) ; 2012CB825503 ; 31271167 ; 2012CBA01304) ; 81271495 ; 81460352) |
引用统计 | |
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 |
推荐引用方式 GB/T 7714 | 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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