Caveolin-1 upregulation in senescent neurons alters amyloid precursor protein processing.
- Author:
Min Ji KANG
1
;
Yoon Hee CHUNG
;
Chang Il HWANG
;
Michiyo MURATA
;
Toyoshi FUJIMOTO
;
In Hee MOOK-JUNG
;
Choong Ik CHA
;
Woong Yang PARK
Author Information
1. Department of Biochemistry and Molecular Biology, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea. wypark@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
aging;
Alzheimer disease;
amyloid beta-protein precursor;
caveolin-1;
neuron
- MeSH:
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
- From:Experimental & Molecular Medicine
2006;38(2):126-133
- CountryRepublic of Korea
- Language:English
-
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.