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Handbook of Neurotoxicity pp 973–993Cite as

Regulation of DA Homeostasis and Role of VMAT2 in DA-Induced Neurodegeneration

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Abstract

Metabolic turnover of dopamine (DA) and other monoamines is tightly regulated by their synthesis, degradation, and compartmentalization. DA transmission plays important roles in learning and behavior, while abnormal DA tone is implicated in multiple neurological disorders, including Parkinson’s disease (PD), schizophrenia, and psychoses. Free cytosolic DA can produce oxidative stress and protein damage and is suspected to contribute to the development of PD. Vesicular monoamine transporter 2 (VMAT2) sequesters DA into synaptic vesicles, thereby occupying a unique position where it facilitates DA synaptic transmission while preventing the deleterious effects of DA presence in the cytosol. This review summarizes recent findings on the regulation of DA cellular homeostasis and on the relationship between VMAT2 activity and DA-mediated neurotoxicity.

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Abbreviations

AADC:

Aromatic l-amino acid decarboxylase

DA:

Dopamine

DAcyt :

Cytosolic DA concentration

DAT:

DA uptake transporter

DOPAC:

3,4-dihydroxyphenylacetate

DOPAL:

3,4-dihydroxyphenylacetaldehyde

LC:

Locus coeruleus

L-DOPA:

l-3,4-dihydroxyphenylalanine, levodopa

MAO:

Monoamine oxidase

METH:

Methamphetamine

MPP+ :

1-methyl-4-phenylpyridinium

MSN:

Medium spiny neurons

PD:

Parkinson’s disease

SNpc:

Substantia nigra pars compacta

ROS:

Reactive oxygen species

TH:

Tyrosine hydroxylase

VGLUT2:

Vesicular glutamate transporter 2

VTA:

Ventral tegmental area

VMAT:

Vesicular monoamine transporter

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Acknowledgments

I thank Drs. David Sulzer and Yvonne Schmitz for their help during the preparation of the manuscript. The project was supported by the Picower Foundation, the Parkinson’s Disease Foundation, and grants number R01NS075222 and R03NS064373 from the National Institute of Neurological Disorders and Stroke.

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  1. Department of Neurology, Columbia University, BB308, 650 W 168th Street, New York, NY, 10032, USA

    Eugene V. Mosharov

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Correspondence to Eugene V. Mosharov .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Mosharov, E.V. (2014). Regulation of DA Homeostasis and Role of VMAT2 in DA-Induced Neurodegeneration. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_2

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