title: Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells.
abstract: 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 β-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-3β) 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-3β 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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKunming, China; Nerve System Coding Discipline Group, Kunming College of Life Science, University of the Chinese Academy of SciencesKunming, China; Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation, Yunnan Bai Yao Group Innovation and R&D Center, Yunnan Institute of Materia MedicaKunming, China.
authors.forename: Xiaping
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKunming, China; Nerve System Coding Discipline Group, Kunming College of Life Science, University of the Chinese Academy of SciencesKunming, China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences Kunming, China.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rizak
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKunming, China; Nerve System Coding Discipline Group, Kunming College of Life Science, University of the Chinese Academy of SciencesKunming, China.
authors.forename: Shihao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences Kunming, China.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of SciencesBeijing, China; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of SciencesBeijing, China.
authors.forename: Rongqiao
authors.initials: R
authors.lastname: He
authors.affiliation: Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation, Yunnan Bai Yao Group Innovation and R&D Center, Yunnan Institute of Materia Medica Kunming, China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences Kunming, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Qin
authors.affiliation: Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation, Yunnan Bai Yao Group Innovation and R&D Center, Yunnan Institute of Materia Medica Kunming, China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKunming, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesShanghai, China; Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of SciencesKunming, China.
authors.forename: Xintian
authors.initials: X
authors.lastname: Hu
keywords: Alzheimer's disease; CaMKII; GSK-3β; PP2A; formaldehyde; resveratrol; tau protein