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Dopamine Homeostasis and Role of VMAT2 in Neurodegeneration

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  • First Online:
Handbook of Neurotoxicity

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Abstract

Dopamine transmission plays important roles in learning and behavior, while abnormal dopaminergic tone is implicated in multiple neurological disorders, including Parkinson’s disease, schizophrenia, and psychoses. As catecholamines are reactive molecules, metabolic turnover of dopamine is tightly regulated by its synthesis, degradation, and compartmentalization. Vesicular monoamine transporter 2 (VMAT2) sequesters dopamine into synaptic vesicles, thereby occupying a unique role by facilitating dopaminergic neurotransmission at the same time preventing the deleterious effects of dopamine presence in the cytosol. This review summarizes recent findings on the regulation of dopamine cellular homeostasis and on the relationship between VMAT2 activity and dopamine-mediated neurotoxicity.

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Abbreviations

AADC:

Aromatic l-amino acid decarboxylase

DA:

Dopamine

DAcyt:

Cytosolic DA

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

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SNpc:

Substantia nigra pars compacta

SPN:

Spiny projection neurons

TH:

Tyrosine hydroxylase

VGLUT2:

Vesicular glutamate transporter 2

VMAT:

Vesicular monoamine transporter

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Acknowledgments

The project was supported by the JPB Foundation and R01 DA07418 and R01 MH108186.

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  1. Departments of Psychiatry and Neurology, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, USA

    Eugene V. Mosharov

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  1. 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, TN, USA

    Richard M. Kostrzewa

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Mosharov, E.V. (2021). Dopamine Homeostasis and Role of VMAT2 in Neurodegeneration. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_2-1

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  • DOI: https://doi.org/10.1007/978-3-030-71519-9_2-1

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