Methylglyoxal-senkende Wirkstoffe als Behandlung der Alzheimer-Krankheit?

Advanced Glycation End Products (AGEs) play a significant role in age-related diseases such as Alzheimer's disease. 1,2-Dicarbonyl compounds, such as glyoxal and methylglyoxal, are involved in the formation of these AGEs. Therefore, the hypothesis was proposed that the progression of Alzheimer's disease could be slowed by reducing the concentration of 1,2-dicarbonyl compounds, which would consequently lead to a decrease in AGE formation. The aim of this work was to establish an HPLC method for the detection of glyoxal and methylglyoxal from cultured cells to determine the potential of various agents to lower the concentration of these 1,2-dicarbonyl compounds. Additionally, it was examined whether ALT-711 (Alagebrium), an AGE-lowering drug, acts as an inhibitor of the enzyme thiamine diphosphokinase due to its structural homology to the natural substrate thiamine of the enzyme. This enzyme is responsible for the formation of thiamine diphosphate, the co-factor of the enzyme transketolase, which is involved in the breakdown of methylglyoxal. Thus, inhibition of thiamine diphosphokinase activity would counteract the primary AGE-lowering effect of ALT-711.