S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biochemistry & Molecular Biology (생화학교실) Journal Papers (저널논문_생화학교실)
Constitutive JAK2/STAT1 activation regulates endogenous BACE1 expression in neurons
- Issue Date
- Biochemical and Biophysical Research Communications 386 (2009) 175-180
- Amyloid Precursor Protein Secretases/*genetics ; Amyloid beta-Protein/metabolism ; Animals ; Aspartic Endopeptidases/*genetics ; Cells, Cultured ; Humans ; Interferon-gamma/pharmacology ; Janus Kinase 2/*metabolism ; Mice ; Neurons/drug effects/*enzymology ; Promoter Regions, Genetic ; STAT1 Transcription Factor/*metabolism ; Gene Expression Regulation, Enzymologic
- The protease BACE1 (beta-site APP-cleaving enzyme 1) is essential for the generation of amyloid beta (Abeta) from amyloid precursor protein (APP). Although BACE1 is expressed primarily in neurons, which are a principal source of Abeta in the brain, the mechanism that underlies basal expression of BACE1 in neurons has not been studied thoroughly. In the present study, we found that endogenous BACE1 expression was mediated by constitutive JAK2/STAT1 activation in neurons. Inhibition of the JAK2/STAT1 signaling pathway, using AG490 (a JAK2 inhibitor), a dominant-negative form of STAT1, and SOCS1 and SOCS3 overexpression, reduced levels of BACE1 promoter activity, expression of endogenous BACE1, and generation of Abeta. These results were recapitulated in the SH-SY5Y neuronal cell line, primary cultured neurons, and mouse brains. Therefore, we propose that constitutive JAK2/STAT1 activation mediates endogenous BACE1 expression in neurons and that inhibition of JAK2/STAT1 signaling abrogates basal levels of BACE1 expression and Abeta generation.
- 1090-2104 (Electronic)
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