VMAT2 and Parkinson’s disease: harnessing the dopamine vesicle

Despite a movement away from dopamine-focused Parkinson's disease (PD) research, a recent surge of evidence now suggests that altered vesicular storage of dopamine may contribute to the demise of the nigral neurons in this disease. Human studies demonstrate that the vesicular monoamine transporter 2 (VMAT2; SLC18A2) is dysfunctional in PD brain. Moreover, studies with transgenic mice suggest that there is an untapped reserve capacity of the dopamine vesicle that could be unbridled by increasing VMAT2 function. Therapeutic manipulation of VMAT2 level or function has the potential to improve efficacy of dopamine derived from administered levodopa, increase dopamine neurotransmission from remaining midbrain dopamine neurons and protect against neurotoxic insults. Thus, the development of drugs to enhance the storage of release of dopamine may be a fruitful avenue of research for PD.