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 microM 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.