Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease

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Abstract

Dopamine (DA)- or L-dihydroxyphenylalanine- (L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reaction induced by longterm L-DOPA therapy but also in the pathogenesis of Parkinson's disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-α-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintaining DA levels. Since tyrosinase also possess catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in long-term L-DOPA-treated Parkinson's disease patients.

Original languageEnglish
Pages (from-to)165-176
Number of pages12
JournalNeurotoxicity Research
Volume5
Issue number3
DOIs
Publication statusPublished - 2003

Fingerprint

Dihydroxyphenylalanine
Monophenol Monooxygenase
Parkinson Disease
Dopamine
Tyrosine 3-Monooxygenase
Dopaminergic Neurons
Quinones
Oxidation
Synucleins
Neurons
Catechols
dopamine quinone
Reactive Nitrogen Species
Melanins
Hydroxyl Radical
Catecholamines
Cell death
Cytotoxicity
Metabolites
Reactive Oxygen Species

Keywords

  • Dopamine
  • L-DOPA
  • Neurotoxicity
  • Parkinson's disease
  • Quinone
  • Tyrosinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

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title = "Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease",
abstract = "Dopamine (DA)- or L-dihydroxyphenylalanine- (L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reaction induced by longterm L-DOPA therapy but also in the pathogenesis of Parkinson's disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-α-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintaining DA levels. Since tyrosinase also possess catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in long-term L-DOPA-treated Parkinson's disease patients.",
keywords = "Dopamine, L-DOPA, Neurotoxicity, Parkinson's disease, Quinone, Tyrosinase",
author = "Masato Asanuma and Ikuko Miyazaki and Norio Ogawa",
year = "2003",
doi = "10.1007/BF03033137",
language = "English",
volume = "5",
pages = "165--176",
journal = "Neurotoxicity Research",
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T1 - Dopamine- or L-DOPA-induced neurotoxicity

T2 - The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease

AU - Asanuma, Masato

AU - Miyazaki, Ikuko

AU - Ogawa, Norio

PY - 2003

Y1 - 2003

N2 - Dopamine (DA)- or L-dihydroxyphenylalanine- (L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reaction induced by longterm L-DOPA therapy but also in the pathogenesis of Parkinson's disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-α-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintaining DA levels. Since tyrosinase also possess catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in long-term L-DOPA-treated Parkinson's disease patients.

AB - Dopamine (DA)- or L-dihydroxyphenylalanine- (L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reaction induced by longterm L-DOPA therapy but also in the pathogenesis of Parkinson's disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-α-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintaining DA levels. Since tyrosinase also possess catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in long-term L-DOPA-treated Parkinson's disease patients.

KW - Dopamine

KW - L-DOPA

KW - Neurotoxicity

KW - Parkinson's disease

KW - Quinone

KW - Tyrosinase

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JO - Neurotoxicity Research

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