Abstract
Dopamine oxidation is proposed to be a significant contributor to mesostriatal dopaminergic neurodegeneration, although the mechanisms are not fully resolved. Recent results from in vitro and in vivo models have suggested that some products from mercapturic acid pathway (MAP) metabolism of oxidized dopamine (DA) may contribute to dopaminergic neurodegeneration, and that at least one product of this pathway, 5-S-cysteinyldopamine (Cys-DA), is elevated in patients with advanced Parkinsons disease (PD). Here we review recent findings on MAP enzymes and their products in rodent brain and in diseased regions of brain from patients with mesostriatal dopaminergic neurodegeneration. We also review the current data and our recent findings on the neurobiological activity of MAP metabolites of oxidized DA. We conclude that human striatum has limited enzymatic capacity for mercapturate formation, that levels of MAP products of oxidized DA are significantly elevated in PD patients with advanced dopaminergic neurodegeneration but not in patients with less severe degeneration, and that Cys-DA interferes with trafficking of DA in vitro and in vivo. These results indicate that Cys-DA may interfere with DA trafficking in patients with advanced dopaminergic neurodegeneration.
Current Topics in Medicinal Chemistry
Title: Dopamine Thioethers in Neurodegeneration
Volume: 1 Issue: 6
Author(s): Kathrin R. Sidell, Ventkataraman Amarnath and Thomas J. Montine
Affiliation:
Abstract: Dopamine oxidation is proposed to be a significant contributor to mesostriatal dopaminergic neurodegeneration, although the mechanisms are not fully resolved. Recent results from in vitro and in vivo models have suggested that some products from mercapturic acid pathway (MAP) metabolism of oxidized dopamine (DA) may contribute to dopaminergic neurodegeneration, and that at least one product of this pathway, 5-S-cysteinyldopamine (Cys-DA), is elevated in patients with advanced Parkinsons disease (PD). Here we review recent findings on MAP enzymes and their products in rodent brain and in diseased regions of brain from patients with mesostriatal dopaminergic neurodegeneration. We also review the current data and our recent findings on the neurobiological activity of MAP metabolites of oxidized DA. We conclude that human striatum has limited enzymatic capacity for mercapturate formation, that levels of MAP products of oxidized DA are significantly elevated in PD patients with advanced dopaminergic neurodegeneration but not in patients with less severe degeneration, and that Cys-DA interferes with trafficking of DA in vitro and in vivo. These results indicate that Cys-DA may interfere with DA trafficking in patients with advanced dopaminergic neurodegeneration.
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Kathrin R. Sidell , Ventkataraman Amarnath and Thomas J. Montine , Dopamine Thioethers in Neurodegeneration, Current Topics in Medicinal Chemistry 2001; 1 (6) . https://dx.doi.org/10.2174/1568026013394705
DOI https://dx.doi.org/10.2174/1568026013394705 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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