TY - JOUR

T1 - GPR39 Zn2+-sensing receptor

T2 - a new target in antidepressant development?

AU - Młyniec, Katarzyna

AU - Singewald, Nicolas

AU - Holst, Birgitte

AU - Nowak, Gabriel

N1 - Copyright © 2014 Elsevier B.V. All rights reserved.

PY - 2015/3/15

Y1 - 2015/3/15

N2 - 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 Zn2+-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 Zn2+-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 Zn2+-sensing receptor may be considered as a new target for drug development in the field of depression.

AB - 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 Zn2+-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 Zn2+-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 Zn2+-sensing receptor may be considered as a new target for drug development in the field of depression.

U2 - 10.1016/j.jad.2014.11.033

DO - 10.1016/j.jad.2014.11.033

M3 - Journal article

C2 - 25490458

VL - 174

SP - 89

EP - 100

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

SN - 0165-0327

ER -