Journal of Alzheimer's Disease vol:20 issue:4 pages:1119-1132
Peroxisome proliferator-activated receptor gamma (PPAR gamma) activation results in an increased rate of amyloid-beta (A beta) clearance from the media of diverse cells in culture, including primary neurons and glial cells. Here, we further investigate the mechanism for A beta clearance and found that PPAR gamma activation modulates a cell surface metalloprotease that can be inhibited by metalloprotease inhibitors, like EDTA and phenanthroline, and also by the peptide hormones insulin and glucagon. The metalloprotease profile of the A beta-degrading mechanism is surprisingly similar to insulin-degrading enzyme (IDE). This mechanism is maintained in hippocampal and glia primary cultures from IDE loss-of-function mice. We conclude that PPAR gamma activates an IDE-like A beta degrading activity. Our work suggests a drugable pathway that can clear A beta peptide from the brain.