Młyniec Katarzyna, Singewald Nicolas, Holst Birgitte, Nowak Gabriel
Department of Biochemical Toxicology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82/III, A-6020 Innsbruck, Austria.
J Affect Disord. 2015 Mar 15;174:89-100. doi: 10.1016/j.jad.2014.11.033. Epub 2014 Nov 26.
Zinc is a trace element released from glutamatergic terminals, and modulates the pre- and postsynaptic areas, giving a diverse biological response. Zinc is a natural ligand that inhibits the N-methyl-d-aspartate (NMDA) receptor and regulates the excessive release of glutamate. Moreover, zinc exhibits an antidepressant-like profile, as demonstrated in both preclinical and clinical studies. Recent reports indicate that the GPR39 Zn(2+)-sensing receptor is an important target for zinc "transmission" (its activation modulates/induces diverse biochemical pathways involved in neuroprotection). Preclinical studies provide evidence that zinc deficiency leads to depressive-like behavior related to down-regulation of the GPR39 Zn(2+)-sensing receptor. Zinc binds to the GPR39 and triggers signals, leading to CRE-dependent gene transcription, resulting in increases in proteins such as brain-derived neurotrophic factor (BDNF), that plays a pivotal role in antidepressant action. Chronic administration of many antidepressants induces GPR39 up-regulation, which suggests that the Zn(2+)-sensing receptor may be considered as a new target for drug development in the field of depression.
锌是一种从谷氨酸能终末释放的微量元素，可调节突触前和突触后区域，产生多种生物学反应。锌是一种天然配体，可抑制N-甲基-D-天冬氨酸（NMDA）受体并调节谷氨酸的过度释放。此外，正如临床前和临床研究所示，锌具有类抗抑郁作用。最近的报告表明，GPR39锌离子感应受体是锌“传递”的重要靶点（其激活可调节/诱导参与神经保护的多种生化途径）。临床前研究提供的证据表明，锌缺乏会导致与GPR39锌离子感应受体下调相关的抑郁样行为。锌与GPR39结合并触发信号，导致依赖于CRE的基因转录，从而使诸如脑源性神经营养因子（BDNF）等蛋白质增加，BDNF在抗抑郁作用中起关键作用。长期服用多种抗抑郁药会诱导GPR39上调，这表明锌离子感应受体可能被视为抑郁症领域药物开发的新靶点。
