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

Cristina D'Abramo, Sara Massone, Jean Marc Zingg, Antonio Pizzuti, Philippe Marambaud, Bruno Dalla Piccola, Angelo Azzi, Umberto M. Marinari, Maria A. Pronzato, Roberta Ricciarelli

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Recent data indicate that PPARγ (peroxisome proliferator-activated receptor γ) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. In the present study we show that PPARγ overexpression in cultured cells dramatically reduced Aβ (amyloid-β) secretion, affecting the expression of the APP (Aβ 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 PPARγ was able to protect the cells from H2O2-induced necrosis by decreasing Aβ secretion. Taken together, our results indicate a novel mechanism at the basis of the neuroprotection shown by PPARγ agonists and an additional pathogenic role for Aβ accumulation.

Original languageEnglish (US)
Pages (from-to)693-698
Number of pages6
JournalBiochemical Journal
Volume391
Issue number3
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein (APP)
  • Amyloid-β
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Peroxisome proliferator-activated receptor γ (PPARγ)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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