Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer's disease.
BMB Rep
; 43(10): 704-9, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-21034535
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 3ß (GSK-3ß), 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Precursor de Proteína beta-Amiloide
/
Enfermedad de Alzheimer
/
Mutación
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
BMB Rep
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2010
Tipo del documento:
Article