GPR39 Zn2+-sensing receptor: a new target in antidepressant development?
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Affective Disorders |
Vol/bind | 174 |
Sider (fra-til) | 89-100 |
Antal sider | 12 |
ISSN | 0165-0327 |
DOI | |
Status | Udgivet - 15 mar. 2015 |
ID: 137292297