Regulation of DA homeostasis and role of VMAT2 in DA-induced neurodegeneration

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.