Department of Biochemistry, Molecular, Cellular Biology and Lombardi Cancer Center, Georgetown University, Washington, DC 20007, United States.
FEBS Lett. 2011 Apr 6;585(7):1001-6. doi: 10.1016/j.febslet.2011.03.009. Epub 2011 Mar 23.
Although well-studied in the context of neurodegenerative disease, a clear biological function for the synuclein proteins remains elusive. Emerging data indicate a role for synucleins in monoamine neurotransmitter homeostasis. A key regulatory component of monoamine neurotransmission is re-uptake of neurotransmitter by the dopamine transporter, norepinephrine transporter, and serotonin transporter, which are common drug targets in the treatment of depression and other mood disorders. Through interactions with these transporters, the neuronal cytoskeleton, and pre-synaptic scaffolding proteins, α-synuclein, β-synuclein, and γ-synuclein modulate trafficking, expression and function of monoamine transporters at the cell surface, thus playing a central role in regulating monoamine re-uptake.
虽然在神经退行性疾病的背景下对突触核蛋白进行了深入研究，但它们的确切生物学功能仍难以捉摸。新出现的数据表明，突触核蛋白在单胺神经递质稳态中起作用。单胺神经递质传递的一个关键调节组成部分是多巴胺转运体、去甲肾上腺素转运体和 5-羟色胺转运体对神经递质的再摄取，这些转运体是治疗抑郁症和其他情绪障碍的常见药物靶点。通过与这些转运体、神经元细胞骨架和突触前支架蛋白的相互作用，α-突触核蛋白、β-突触核蛋白和 γ-突触核蛋白调节单胺转运体在细胞表面的运输、表达和功能，从而在调节单胺再摄取中发挥核心作用。
