Caveolin-1 upregulation in senescent neurons alters amyloid precursor protein processing

• Published in: Experimental & molecular medicine Vol. 38; no. 2; pp. 126 - 133
• Main Authors: Kang, Min Ji, Chung, Yoon Hee, Hwang, Chang Il, Murata, Michiyo, Fujimoto, Toyoshi, Mook-Jung, In Hee, Cha, Choong Ik, Park, Woong Yang
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 30.04.2006
• Subjects: Aged; Aged, 80 and over; Aging - metabolism; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Animals; Brain - metabolism; Brain - pathology; Brain - ultrastructure; Caveolae - metabolism; Caveolae - ultrastructure; Caveolin 1 - metabolism; Caveolin 1 - physiology; Humans; Microscopy, Electron; Middle Aged; Protease Nexins; Protein Kinase C - metabolism; Rats; Receptors, Cell Surface - metabolism; Up-Regulation
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/emm.2006.16

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.