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Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2008 Aug 15; Vol. 86 (11), pp. 2476-87. - Publication Year :
- 2008
-
Abstract
- Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease. In this study, we report that the expressions of Swedish double mutation of amyloid precursor protein (Swe-APP) or of the APP intracellular domain (AICD) into nerve growth factor (NGF)-differentiated PC12 cells or rat primary cortical neurons increased mRNA and protein levels of cyclin D1 and cyclin B1. Treatment with lithium chloride (a glycogen synthase kinase-3beta inhibitor) down-regulated cyclin B1 induced by Swe-APP expression but up-regulated cyclin D1 expression induced by Swe-APP, suggesting that glycogen synthase kinase-3beta activity is involved in these expression changes of cyclins D1 and B1. Swe-APP, which is a prevailing cause of familial Alzheimer's disease, is well known to increase amyloid beta peptide production both in vitro and in vivo, but the underlying molecular means whereby it leads to the pathogenesis of AD remains unknown. The finding that cyclin D1 and B1 expressions were up-regulated by Swe-APP in in vitro cultured cells was substantiated in the brain tissues of Tg2576 mice, which harbor the Swe-APP mutation. These results suggest that some disturbances in cell cycle regulation may be involved in Swe-APP or AICD-induced neurodegeneration and that these contribute to the pathogenesis of AD.
- Subjects :
- Alzheimer Disease genetics
Alzheimer Disease physiopathology
Animals
Blotting, Western
Brain physiopathology
Cell Cycle physiology
Cyclin B drug effects
Cyclin B1
Cyclin D1 drug effects
Enzyme Inhibitors pharmacology
Humans
Immunohistochemistry
Immunoprecipitation
Mice
Mice, Transgenic
Mutation
Neurons drug effects
PC12 Cells
Rats
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation
Amyloid beta-Protein Precursor genetics
Brain metabolism
Cyclin B biosynthesis
Cyclin D1 biosynthesis
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4547
- Volume :
- 86
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 18438935
- Full Text :
- https://doi.org/10.1002/jnr.21690