in Title
  in Authors
  in Institutions
  in Abstract
  in Keywords

  - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
  - Instructions to Authors
   "sample paper download"

  - Preparation of Tables
    and Illustrations


  - Chemical and
    Mathematical Usage,
    Addreviations, and
    Symbols


  - Editorial Board

  - Manuscript submission
   form


 



Article Info.
2010.10.31; 43(10) pp. 704~709
Title

Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer¡¯s disease  

Authors

Jongyeon Shin1,2,#, Saet-Byeol Yu1,2,#, Un Young Yu3,#, Sangmee Ahn Jo4 & Jung-Hyuck Ahn3,*  

Institutions

1Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, 2Psoma Therapeutics, Inc., Seoul 110-799, 3Department of Biochemistry, Ewha Womans University School of Medicine, Seoul 158-710, 4Division of Brain Disease, Center for Biomedical Research, National Institute of Health, Korea Center for Disease Control and Prevention, Seoul 122-701, Korea  

Abstract

The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer¡¯s disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase 3¥â (GSK-3¥â), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis. [BMB reports 2010; 43(10): 704-709]
 

Keywords

Alzheimer's disease, Gene expression, Swedish mutation, Tau protein, Transcriptome sequencing