Neurotoxicity Research

, Volume 1, Issue 3, pp 181–195

Intraneuronal dopamine-quinone synthesis: A review

Article

DOI: 10.1007/BF03033289

Cite this article as:
Sulzer, D. & Zecca, L. neurotox res (1999) 1: 181. doi:10.1007/BF03033289

Abstract

Dopamine-quinone is synthesized by oxidation of the catechol ring of dopamine. If this occurs within the neuronal cytosol, the quinone may react with cytosolic components, particularly cysteine residues. In contrast, if quinone is produced within neuronal lysosomes it may provide the fundamental building block for neuromelanin. Since the population of neurons that die in Parkinson’s disease are those that display obvious intralysosomal neuromelanin and since cytosolic dopamine-dependent oxyradical formation may underlie methamphetamine toxicity and other specific forms of neurodegeneration in dopaminergic neurons, it is important to elucidate the pathways leading to dopamine-quinone. Here we review pathways by which intracellular catechols may be oxidized to quinones, either enzymatically or via reduction of ferric iron or other metals. These metabolites can be adduced by cysteine, could underlie aberrant metabolism and ubiquitination pathways, may induce Lewy body formation, and mediate the synthesis of hydroxyl radical and oxyradical species. Finally, we suggest that by accumulating excess cytosolic catecholamine, neuromelanin synthesis may safely sequester quinones that would otherwise be produced in neuronal cytosol.

Keywords

Neuromelanin Parkinson’s disease Lewy bodies Methamphetamine Oxidative stress VMAT Substantia nigra Tyrosinase 

Abbreviations

AD

Alzheimer’s disease

BDNF

brain-derived neurotrophic factor

CNS

central nervous system

DA

dopamine

DAT

dopamine transporter (plasma membrane)

DHBT

dihydrobenzothiazine

DLBD

diffuse Lewy body disease

DOPAC

dihydroxyphenylacetic acid

GDNF

glial-derived neurotrophic factor

HPETE

arachidonic acid hydroperoxide

LBs

Lewy bodies

L-NAC

L-n-acetylcysteine

L-DOPA

L-3,4-dihydroxyphenylalanine

mRNA

messenger RNA

METH

methamphetamine

MPTP

l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine

NE

norepinephrine

NM

neuromelanin

PD

Parkinson’s Disease

PKC

protein kinase C

RT-PCR

reverse transcription polymerase chain reaction

SN

substantia nigra

SNC

substantia nigra pars compacta

SOD

superoxide dismutase

TH

tyrosine hydroxylase

VMAT1

peripheral vesicular monoamine transporter

VMAT2

central vesicular monoamine transporter

VTA

ventral tegmental area

6-OHDA

6-hydroxydopamine

Copyright information

© OPA (Overseas Publishers Association) N.V 2000

Authors and Affiliations

  1. 1.Department of Neurology and PsychiatryColumbia University, New York State Psychiatric InstituteNew YorkUSA
  2. 2.Department of NeuroscienceColumbia University, New York State Psychiatric InstituteNew YorkUSA
  3. 3.Institute of Advanced Biomedical TechnologiesCNRSegrateItaly

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