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Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 6, 2013

Role of peroxisome proliferator-activated receptor gamma in amyloid precursor protein processing and amyloid

Cristina d'Abramo1, Sara Massone, Jean-Marc Zingg

  • 1Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.

The Biochemical Journal
|June 11, 2005
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARgamma) reduces amyloid-beta (Abeta) secretion in cells, suggesting a novel neuroprotective mechanism against Alzheimer's disease progression.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Emerging data suggest peroxisome proliferator-activated receptor gamma (PPARgamma) involvement in Alzheimer's disease pathogenesis.
  • The amyloid cascade is a key pathway in Alzheimer's disease, involving amyloid-beta (Abeta) accumulation.

Purpose of the Study:

  • To investigate the role of PPARgamma in modulating Abeta secretion and its potential neuroprotective effects.
  • To elucidate the molecular mechanisms by which PPARgamma influences Abeta precursor protein (APP) processing.

Main Methods:

  • Overexpression of PPARgamma in cultured cells.
  • Analysis of Abeta secretion levels.
  • Assessment of APP expression and post-transcriptional modifications.
  • Evaluation of cellular protection against hydrogen peroxide (H(2)O(2))-induced necrosis.

Main Results:

  • PPARgamma overexpression significantly reduced Abeta secretion in cultured cells.
  • APP down-regulation occurred at a post-transcriptional level, independent of secretase pathways.
  • Increased APP ubiquitination was observed, correlating with PPARgamma activity.
  • PPARgamma-mediated reduction in Abeta secretion protected cells from H(2)O(2)-induced necrosis.

Conclusions:

  • PPARgamma plays a novel role in reducing Abeta accumulation by affecting APP processing at a post-transcriptional level.
  • PPARgamma agonists may offer neuroprotection in Alzheimer's disease through decreased Abeta secretion.
  • Abeta accumulation contributes to the pathogenesis of neurodegenerative conditions, highlighting a potential therapeutic target.

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