[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5483/BMBRep.2010.43.10.704

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

Shin, Jong-Yeon (Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University)
Yu, Saet-Byeol (Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University)
Yu, Un-Young (Department of Biochemistry, Ewha Womans University School of Medicine)
Ahnjo, Sang-Mee (Division of Brain Disease, Center for Biomedical Research, National Institute of Health, Korea Center for Disease Control and Prevention)
Ahn, Jung-Hyuck (Department of Biochemistry, Ewha Womans University School of Medicine)

Publication Information

BMB Reports / v.43, no.10, 2010 , pp. 704-709 More about this Journal

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 $3\beta$ (GSK-3 $\beta$ ), 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.

Keywords

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

Citations & Related Records

Times Cited By Web Of Science : 3 (Related Records In Web of Science)
Times Cited By SCOPUS : 5

Reference
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2	/ Journal of Alzheimer's Disease
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5	/ Biochemical and Biophysical Research Communications