Contribution of inflammatory processes to Alzheimer's disease: Molecular mechanisms

  • Sastre M
  • Klockgether T
  • Heneka M
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Abstract

There is compelling evidence that Alzheimer's disease (AD) amyloid-β (Aβ) deposition is associated with a local inflammatory response, which is initiated by the activation of microglia and the recruitment of astrocytes. These cells secrete a number of cytokines and neurotoxic products that may contribute to neuronal degeneration and cell death. It has been documented that long-term intake of non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk for developing AD and delay the onset of the disease. The mechanism behind these NSAIDs is still controversial and several hypotheses have been raised, including changes in the amyloid precursor protein (APP) metabolism, in Aβ aggregation and a decrease in inflammatory mediators. Recently, it was proposed that some NSAIDs might activate the peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ belongs to a family of nuclear receptors that are able to regulate the transcription of pro-inflammatory molecules, such as iNOS. The activation of PPAR-γ has been recently reported to reduce Aβ levels in cell culture and AD animal models. The implication of PPAR-γ in the control of Aβ-induced inflammation suggests a new target for AD therapy and emphasize the contribution of neuroinflammatory mechanisms to the pathogenesis of AD. © 2005 ISDN. Published by Elsevier Ltd. All rights reserved.

Author-supplied keywords

  • Alzheimer's disease
  • BACE
  • Inflammation
  • NSAIDs
  • PPARγ

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Authors

  • Michael HenekaRheinische Friedrich-Wilhelms-University Bonn

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  • Magdalena Sastre

  • Thomas Klockgether

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