Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death

Recent data indicate that PPAR gamma (peroxisome proliferator-activated receptor gamma) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. In the present study we show that PPAR gamma overexpression in cultured cells dramatically reduced A beta (amyloid-beta) secretion, affecting the expression of the APP (A beta precursor protein) at a post-transcriptional level. APP down-regulation did not involve the pathway of the secretases, and correlated with a significant induction of APP ubiquitination. Additionally, we demonstrate that PPAR gamma was able to protect the cells from H2O2-induced necrosis by decreasing A beta secretion. Taken together, our results indicate a novel mechanism at the basis of the neuroprotection shown by PPAR gamma agonists and an additional pathogenic role for A beta accumulation.