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.
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Ligand Docking and Structure-based Virtual Screening in Drug Discovery
Current Topics in Medicinal Chemistry Heterocyclic Curcumin Derivatives of Pharmacological Interest: Recent Progress
Current Topics in Medicinal Chemistry Computational Modeling of Dielectrophoretic Microfluidic Channel for Simultaneous Separation of Red Blood Cells and Platelets
Current Signal Transduction Therapy Di / tri-Peptide Transporters as Drug Delivery Targets: Regulation of Transport Under Physiological and Patho-physiological Conditions
Current Drug Targets Modulation of Collagen Turnover in Cardiovascular Disease
Current Pharmaceutical Design Psychosocial Vulnerability and Early Life Adversity as Risk Factors for Central Sensitivity Syndromes
Current Rheumatology Reviews Colon Targeted Pulsatile Drug Delivery System of Venlafaxine Hydrochloride for Treatment of Depression
Current Psychopharmacology Cerebrovascular Profile Assessment in Parkinson's Disease Patients
CNS & Neurological Disorders - Drug Targets Vascular Endothelial Growth Factor in Central Nervous System Injuries – A Vascular Growth Factor Getting Nervous?
Current Neurovascular Research The Molecular Basis of Conantokin Antagonism of NMDA Receptor Function
Current Drug Targets Storage, Expression and Function of Fas Ligand, the Key Death Factor of Immune Cells
Current Medicinal Chemistry 3D Structural Conformation and Functional Domains of Polysialyltransferase ST8Sia IV Required for Polysialylation of Neural Cell Adhesion Molecules
Protein & Peptide Letters The Impacts of Some Sedative Drugs on α -Glycosidase, Acetylcholinesterase and Butyrylcholinesterase Enzymes-potential Drugs for Some Metabolic Diseases
Letters in Drug Design & Discovery Endothelial Chemokines in Autoimmune Disease
Current Pharmaceutical Design A Role for Leptin in the Systemic Inflammatory Response Syndrome (SIRS) and in Immune Response, an Update
Current Medicinal Chemistry Immunotherapy for Drug Abuse
CNS & Neurological Disorders - Drug Targets Assessment of Motor Function in Complex Regional Pain Syndrome With Virtual Reality-based Mirror Visual Feedback: A Pilot Case Study
Neuroscience and Biomedical Engineering (Discontinued) Metabotropic Glutamate Receptor 5 in Down's Syndrome Hippocampus During Development: Increased Expression in Astrocytes
Current Alzheimer Research GABA Targets for the Treatment of Cognitive Dysfunction in Schizophrenia
Current Neuropharmacology Medicinal Chemistry Perspective of Fused Isoxazole Derivatives
Current Topics in Medicinal Chemistry