Decrease of dehydrogenase activity of cerebral glyceraldehyde-3-phosphate dehydrogenase in different animal models of Alzheimer's disease

Biochim Biophys Acta. 2007 May;1770(5):826-32. doi: 10.1016/j.bbagen.2007.01.014. Epub 2007 Feb 4.

Abstract

Recently, a relationship between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the beta-amyloid precursor protein (betaAPP) in relationship with the pathogenesis of Alzheimer's disease (AD) has been suggested. Therefore, we studied the specific activity of GAPDH in the different animal models of AD: transgenic mice (Tg2576) and rats treated with beta-amyloid, or thiorphan, or lipopolysaccharides (LPS) and interferon gamma (INFgamma). We observed that GAPDH activity was significantly decreased in the brain samples from TG mice. The injection of beta-amyloid, or thiorphan, an inhibitor of neprilysin involved in beta-amyloid catabolism, in rat brains resulted in a pronounced reduction of the enzyme activity. The infusion of LPS and IFNgamma, which can influence the progression of the AD, significantly reduced the enzyme activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / genetics*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Disease Models, Animal
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / analysis
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / isolation & purification
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • Humans
  • Infusion Pumps
  • Injections, Intraventricular
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / toxicity
  • Male
  • Maze Learning
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neprilysin / antagonists & inhibitors
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / genetics*
  • Peptide Fragments / metabolism
  • Rats
  • Rats, Inbred F344
  • Telencephalon / enzymology*
  • Telencephalon / metabolism*
  • Thiorphan / administration & dosage
  • Thiorphan / pharmacology

Substances

  • Amyloid beta-Peptides
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Interferon-gamma
  • Thiorphan
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Neprilysin