title: DNA Demethylation Upregulated Nrf2 Expression in Alzheimer's Disease Cellular Model.
abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor in the defense against oxidative stress. Cumulative evidence has shown that oxidative stress plays a key role in the pathogenesis of Alzheimer's disease (AD). Previous animal and clinical studies had observed decreased expression of Nrf2 in AD. However, the underlying regulation mechanisms of Nrf2 in AD remain unclear. Here, we used the DNA methyltransferases (Dnmts) inhibitor 5-aza-2'-deoxycytidine (5-Aza) to test whether Nrf2 expression was regulated by methylation in N2a cells characterizing by expressing human Swedish mutant amyloid precursor protein (N2a/APPswe). We found 5-Aza treatment increased Nrf2 at both messenger RNA and protein levels via downregulating the expression of Dnmts and DNA demethylation. In addition, 5-Aza-mediated upregulation of Nrf2 expression was concomitant with increased nuclear translocation of Nrf2 and higher expression of Nrf2 downstream target gene
  quinone oxidoreductas (NQO1). Our study showed that DNA demethylation promoted the Nrf2 cell signaling pathway, which may enhance the antioxidant system against AD development.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Bio-therapy and Hemato-oncology, Chongqing Cancer Institute , Chongqing , China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Reproductive Biology, Chongqing Medical University , Chongqing , China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yushuang
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
keywords: Alzheimer’s disease; DNA demethylation; NQO1; Nrf2; cellular model; oxidative stress