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Intraneuronal dopamine-quinone synthesis: A review

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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.

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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

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Authors and Affiliations

  1. Department of Neurology and Psychiatry, Columbia University, New York State Psychiatric Institute, Black Building, room 305, 650 West 168th St., 10032, New York, NY, USA

    David Sulzer

  2. Department of Neuroscience, Columbia University, New York State Psychiatric Institute, Black Building, room 305, 650 West 168th St., 10032, New York, NY, USA

    David Sulzer & Luigi Zecca

  3. Institute of Advanced Biomedical Technologies, CNR, 20090, Segrate, Italy

    Luigi Zecca

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  1. David Sulzer
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Correspondence to David Sulzer.

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Sulzer, D., Zecca, L. Intraneuronal dopamine-quinone synthesis: A review. neurotox res 1, 181–195 (1999). https://doi.org/10.1007/BF03033289

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