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.
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