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首页> 外文期刊>The European Journal of Neuroscience >Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease
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Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease

机译：作为突触多巴胺动态的膜转运蛋白：对疾病的影响

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Dopamine was first identified as a neurotransmitter localized to the midbrain over 50years ago. The dopamine transporter (DAT; SLC6A3) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2) are regulators of dopamine homeostasis in the presynaptic neuron. DAT transports dopamine from the extracellular space into the cytosol of the presynaptic terminal. VMAT2 then packages this cytosolic dopamine into vesicular compartments for subsequent release upon neurotransmission. Thus, DAT and VMAT2 act in concert to move the transmitter efficiently throughout the neuron. Accumulation of dopamine in the neuronal cytosol can trigger oxidative stress and neurotoxicity, suggesting that the proper compartmentalization of dopamine is critical for neuron function and risk of disease. For decades, studies have examined the effects of reduced transporter function in mice (e.g. DAT-KO, VMAT2-KO, VMAT2-deficient). However, we have only recently been able to assess the effects of elevated transporter expression using BAC transgenic methods (DAT-tg, VMAT2-HI mice). Complemented with invitro work and neurochemical techniques to assess dopamine compartmentalization, a new focus on the importance of transporter proteins as both models of human disease and potential drug targets has emerged. Here, we review the importance of DAT and VMAT2 function in the delicate balance of neuronal dopamine.
机译：50多年前，多巴胺首次被确定为一种局限于中脑的神经递质。多巴胺转运体（DAT；SLC6A3）和囊泡单胺转运体2（VMAT2；SLC18A2）是突触前神经元多巴胺稳态的调节器。DAT将多巴胺从细胞外空间运输到突触前终末的细胞质中。然后，VMAT2将这种胞浆多巴胺包装到囊泡室中，以便在神经传递时释放。因此，DAT和VMAT2协同作用，在整个神经元中有效地移动递质。多巴胺在神经元胞浆中的积累可引发氧化应激和神经毒性，表明多巴胺的适当区隔对神经元功能和疾病风险至关重要。几十年来，研究已经检测了小鼠转运体功能降低的影响（例如DAT-KO、VMAT2-KO、VMAT2缺陷）。然而，我们直到最近才能够使用BAC转基因方法（DAT-tg、VMAT2-HI小鼠）评估转运体表达升高的影响。通过体外研究和神经化学技术来评估多巴胺的区隔化，一个新的焦点出现在转运蛋白作为人类疾病模型和潜在药物靶点的重要性上。在这里，我们回顾了DAT和VMAT2功能在神经多巴胺微妙平衡中的重要性。

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