Exp Mol Med.
2006 Apr;38(2):126-133.
Caveolin-1 upregulation in senescent neurons alters amyloid precursor protein processing
- Affiliations
-
- 1Department of Biochemistry and Molecular Biology, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea. wypark@snu.ac.kr
- 2Department of Anatomy, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.
- 3Ilchun Molecular Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.
- 4Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Abstract
- Lipid rafts provide a platform for regulating cellular functions and participate in the pathogenesis of several diseases. However, the role of caveolin-1 in this process has not been elucidated definitely in neuron. Thus, this study was performed to examine whether caveolin-1 can regulate amyloid precursor protein (APP) processing in neuronal cells and to identify the molecular mechanisms involved in this regulation. Caveolin-1 is up-regulated in all parts of old rat brain, namely hippocampus, cerebral cortex and in elderly human cerebral cortex. Moreover, detergent-insoluble glycolipid (DIG) fractions indicated that caveolin-1 was co-localized with APP in caveolae-like structures. In DIG fractions, bAPP secretion was up-regulated by caveolin-1 over-expression, which was modulated via protein kinase C (PKC) in neuroblastoma cells. From these results we conclude that caveolin-1 is selectively expressed in senescent neurons and that it induces the processing of APP by beta-secretase via PKC downregulation.
MeSH Terms
-
Up-Regulation
Receptors, Cell Surface/*metabolism
Rats
Protein Kinase C/metabolism
Middle Aged
Microscopy, Electron
Humans
Caveolin 1/*metabolism/physiology
Caveolae/*metabolism/ultrastructure
Brain/metabolism/pathology/ultrastructure
Animals
Amyloid beta-Protein Precursor/*metabolism
Amyloid beta-Protein/*metabolism
Alzheimer Disease/*metabolism
Aging/metabolism
Aged, 80 and over
Aged
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- A Newer Therapeutic Strategies For Alzheimer's Disease
- Molecular Genetic Aspects of Alzheimer's Disease
- Immunohistochemical Study on GTP-binding Rab6 Expression in the Hippocampal Cortices of the Alzheimer Brain
- Zinc Inhibits Amyloid beta Production from Alzheimer's Amyloid Precursor Protein in SH-SY5Y Cells
- Effect of Ischemic Neuronal Insults on Amyloid Precursor Protein Processing
