Neurotoxicity Research

, Volume 7, Issue 1, pp 95–101

The carbonyl scavengers aminoguanidine and tenilsetam protect against the neurotoxic effects of methylglyoxal

Authors

  • Julie Webster
    • Comparative Genomics CentreJames Cook University
  • Christin Urban
    • Comparative Genomics CentreJames Cook University
  • Katrin Berbaum
    • Comparative Genomics CentreJames Cook University
  • Claudia Loske
    • Neuroimmunological Cell Biology Unit, IZKFUniversität Leipzig
  • Alan Alpar
    • Dept. of Neuro anatomy, Paul-Flechsig-Institute for Brain ResearchUniversity of Leipzig
  • Ulrich GÄrtner
    • Dept. of Neuro anatomy, Paul-Flechsig-Institute for Brain ResearchUniversity of Leipzig
  • Susana Garcia De Arriba
    • Neuroimmunological Cell Biology Unit, IZKFUniversität Leipzig
  • Thomas Arendt
    • Dept. of Neuro anatomy, Paul-Flechsig-Institute for Brain ResearchUniversity of Leipzig
    • Comparative Genomics CentreJames Cook University
    • Neuroimmunological Cell Biology Unit, IZKFUniversität Leipzig
Article

DOI: 10.1007/BF03033780

Cite this article as:
Webster, J., Urban, C., Berbaum, K. et al. neurotox res (2005) 7: 95. doi:10.1007/BF03033780

Abstract

Advanced glycation end products (AGEs) have been identified in age-related intracellular protein deposits of Alzheimer’s disease (amyloid plaques and neurofibrillary tangles) and Parkinson disease (Lewy bodies), suggesting that these protein deposits have been exposed to AGE precursors such as the reactive dicarbonyl compound methylglyoxal. In ageing tissue and under diabetic pseudohypoxia, intracellular methylglyoxal levels rise through an impairment of triosephosphate utilization. Furthermore, methylglyoxal detoxification is impaired when reduced glutathione levels are low, conditions, which have all been described in Alzheimer’s disease. However, there is less known about the toxicity of methylglyoxal, particularly about therapeutic strategies to scavenge such dicarbonyl compounds and attenuate their toxicity. In our study, extracellularly applied methylglyoxal was shown to be toxic to human neuroblastoma cells in a dose-dependent manner above concentrations of 150 µM with a LD50 of approximately 1.25 mM. Pre-incubation of methylglyoxal with a variety of carbonyl scavengers such as aminoguanidine or tenilsetam and the thiol antioxidant lipoic acid significantly reduced its toxicity. In summary, carbonyl scavengers might offer a promising therapeutic strategy to reduce the neurotoxicity of reactive carbonyl compounds, providing a potential benefit for patients with age-related neurodegenerative diseases.

Keywords

Methylglyoxal Carbonyl stress Aminoguanidine Tenilsetam Lipoic acid Neurotoxicity

Copyright information

© Springer 2005