title: Role of peroxisome proliferator-activated receptor gamma in amyloid precursor protein processing and amyloid beta-mediated cell death.
abstract: Recent data indicate that PPARgamma (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 PPARgamma overexpression in cultured cells dramatically reduced Abeta (amyloid-beta) secretion, affecting the expression of the APP (Abeta 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 PPARgamma was able to protect the cells from H(2)O(2)-induced necrosis by decreasing Abeta secretion. Taken together, our results indicate a novel mechanism at the basis of the neuroprotection shown by PPARgamma agonists and an additional pathogenic role for Abeta accumulation.
authors.affiliation: Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: d'Abramo
authors.forename: Sara
authors.initials: S
authors.lastname: Massone
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Zingg
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Philippe
authors.initials: P
authors.lastname: Marambaud
authors.forename: Bruno
authors.initials: B
authors.lastname: Dalla Piccola
authors.forename: Angelo
authors.initials: A
authors.lastname: Azzi
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Marinari
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D006861:Hydrogen Peroxide; D009336:Necrosis; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D034622:RNA Interference
chemical_list: D016564:Amyloid beta-Protein Precursor; D047495:PPAR gamma; D006861:Hydrogen Peroxide