TY - JOUR TI - Potential role of methylglyoxal in inducing Parkinson’s disease DO - https://doi.org/doi:10.7282/T3HH6NHS PY - 2017 AB - About one and a half million people are affected by Parkinson’s disease (PD) in the United States. It is a neurodegenerative disorder on dopaminergic neurons in the substantia nigra pars compacta, with primary effects on motion disorder. The causes for the Parkinsonism are generally divide into genetic factors like mutation and environmental factors like heavy metals as well as some endogenous or exogenous agents. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and other MPTP-like neurotoxins such as salsolinol are well known and considered to cause Parkinsonism due to their in vivo metabolic products’ specific toxicity for dopaminergic neurons. Recent studies showed that the diabetic patient is more likely to develop the Parkinson’s disease. It has been suspected that the methylglyoxal, one metabolic product of glycolysis, is associated with this phenomenon because the body concentration of methylglyoxal for diabetic patients will be three to six times higher than healthy people. The dopamine-derived tetrahydroisoquinoline (TIQ), 1-acetyl-6,7-dihydroxyl-1,2,3,4-tetrahydro- isoquinoline (ADTIQ), has been detected in frozen brain tissue of human with Parkinson’s disease. It can be produced by the reaction of dopamine and methylglyoxal in physiological condition and has been regarded a novel endogenous neurotoxins. In our study, in addition to ADTIQ, 6,7-dihydroxy-1,2,3,4-tetrahydro- isoquinoline or called norsalsolinol was also detected in the reaction system of dopamine and methylglyoxal by LC-MS/MS. And based on the Pictect-Spengler reaction, there are two regioselectivities for the products under neutral conditions. So there are two isomers for both ADTIQ and norsalsolinol. Additionally, according to the proposed reaction mechanism, the norsalsolinol was generated from ADTIQ by deacylation. On the other hand, with different ratios of dopamine and methylglyoxal, different levels of reaction under the physiological condition were also monitored by HPLC-UV. It revealed that when the ratio of dopamine and methylglyoxal is over 1:10, the reaction could almost be completed within 24 hours. In conclusion, we showed for the first time that the potential neurotoxin norsalsolinol could be generated through the reaction of dopamine and methylglyoxal. And also can be one reason why the norsalsolinol was detected in the frozen brain of humans. KW - Food Science KW - Parkinson's disease LA - eng ER -