Dopamine Homeostasis and Role of VMAT2 in Neurodegeneration

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.