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

Exp Mol Med. 2006 Apr 30;38(2):126-33. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Caveolin 1
  • Protease Nexins
  • Receptors, Cell Surface
  • Protein Kinase C