Bernstein Alison I, Stout Kristen A, Miller Gary W
Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322, USA; Department of Pharmacology, Emory University, Atlanta, GA 30322, USA; Department of Neurology, Emory University, Atlanta, GA 30322, USA.
Neurochem Int. 2014 Jul;73:89-97. doi: 10.1016/j.neuint.2013.12.003. Epub 2014 Jan 4.
Active transport of neurotransmitters into synaptic vesicles is required for their subsequent exocytotic release. In the monoamine system, this process is carried out by the vesicular monoamine transporters (VMAT1 and VMAT2). These proteins are responsible for vesicular packaging of dopamine, norepinephrine, serotonin, and histamine. These proteins are essential for proper neuronal function; however, compared to their plasma membrane counterparts, there are few drugs available that target these vesicular proteins. This is partly due to the added complexity of crossing the plasma membrane, but also to the technical difficulty of assaying for vesicular uptake in high throughput. Until recently, reagents to enable high throughput screening for function of these vesicular neurotransmitter transporters have not been available. Fortunately, novel compounds and methods are now making such screening possible; thus, a renewed focus on these transporters as potential targets is timely and necessary.
神经递质向突触小泡的主动转运是其随后胞吐释放所必需的。在单胺系统中，这一过程由囊泡单胺转运体（VMAT1和VMAT2）完成。这些蛋白质负责多巴胺、去甲肾上腺素、5-羟色胺和组胺的囊泡包装。这些蛋白质对正常的神经元功能至关重要；然而，与它们在质膜上的对应物相比，针对这些囊泡蛋白的药物很少。这部分是由于穿过质膜的复杂性增加，也由于高通量检测囊泡摄取的技术难度。直到最近，还没有用于高通量筛选这些囊泡神经递质转运体功能的试剂。幸运的是，新型化合物和方法现在使这种筛选成为可能；因此，重新将这些转运体作为潜在靶点加以关注是及时且必要的。
