Dopamine-Derived Isoquinolines as Dopaminergic Neurotoxins and Oxidative Stress
Oxygen radicals have been proposed as one of the major factors in neural degeneration in the brain (Youdim et al., 1989; Goetz et al., 1990). In Parkinson’s disease (PD) the involvement of oxygen radicals to the cell death of dopamine (DA) neurons has been strongly suggested. The nigrostriatal system should have specific conditions to increase the vulnerability to oxidative stress, such as high turnover of DA and high consumption of oxygen, and elevated levels of iron and copper. Oxidation of DA by monoamine oxidase [monoamine:oxygen oxidoreductase (deaminating), EC 18.104.22.168, MAO], produces hydrogen peroxide and further free radicals. In addition, autoxidation of DA produces oxygen radicals (Fornstedt et al., 1990). Recent studies on a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), reveal that oxidation of MPTP into 1-methyl-4-phenylpyridinium ion (MPP+) by type B MAO is essentially required for the selective neurotoxicity. MPP+ inhibits the oxidative phosphorylation at Complex I of the respiratory chain (Mizuno et al., 1987). In addition, MPP+ releases DA into extracellular space and by its autoxidation free radicals are produced in the brain (Chiueh et al., 1992). These results suggest that production of active oxygen species may be directly involved in the cytotoxicity of neurotoxins.
KeywordsHigh Performance Liquid Chromatography Dopamine Neurol Alkaloid Monoamine
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