Caveolin-1 upregulation in senescent neurons alters amyloid precursor protein processing.
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, beta APP 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.
Kang
Min Ji
MJ
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Chung
Yoon Hee
YH
Hwang
Chang Il
CI
Murata
Michiyo
M
Fujimoto
Toyoshi
T
Mook-Jung
In Hee
IH
Cha
Choong Ik
CI
Park
Woong Yang
WY