Vesicular monoamine transporter (VMAT) regional expression and roles in pathological conditions

Vesicular monoamine transporters (VMATs) are key regulators of neurotransmitter release responsible for controlling numerous physiological, cognitive, emotional, and behavioral functions. They represent important therapeutic targets for numerous pathological conditions. There are two isoforms of VMAT transporter proteins that function as secondary active transporters into the vesicle for storage and release via exocytosis: VMAT1 (SLC18A1) and VMAT2 (SLC18A2) which differ in their function, quantity, and regional expression. VMAT2 has gained considerable interest as a therapeutic target and diagnostic marker. Inhibitors of VMAT2 have been used as an effective therapy for a range of pathological conditions. Additionally, the functionality and phenotypic classification of classical and nonclassical catecholaminergic neurons are identified by the presence of VMAT2 in catecholaminergic neurons. Dysregulation of VMAT2 is also implicated in many neuropsychiatric diseases. Despite the complex role of VMAT2, many aspects of its function remain unclear. Therefore, our aim is to expand our knowledge of the role of VMAT with a special focus on VMAT2 in different systems and cellular pathways which may potentially facilitate development of novel, more specific therapeutic targets. The current review provides a summary demonstrating the mechanism of action of VMAT, its functional role, and its contribution to disease progression and utilization as therapeutic targets.