Antidepressive effects of targeting ELK-1 signal transduction.

作者: Kallia Apazoglou , Severine Farley , Victor Gorgievski , Raoul Belzeaux , Juan Pablo Lopez

DOI: 10.1038/S41591-018-0011-0

关键词:

摘要: Depression, a devastating psychiatric disorder, is leading cause of disability worldwide. Current antidepressants address specific symptoms the disease, but there vast room for improvement 1 . In this respect, new compounds that act beyond classical to target signal transduction pathways governing synaptic plasticity and cellular resilience are highly warranted2-4. The extracellular signal-regulated kinase (ERK) pathway implicated in mood regulation5-7, its pleiotropic functions lack specificity prohibit optimal drug development. Here, we identified transcription factor ELK-1, an ERK downstream partner 8 , as signaling module pathophysiology treatment depression can be targeted independently ERK. ELK1 mRNA was upregulated postmortem hippocampal tissues from depressed suicides; blood samples individuals, failure reduce expression associated with resistance treatment. mice, ELK-1 overexpression per se produced depressive behaviors; conversely, selective inhibition activation prevented depression-like molecular, behavioral states induced by stress. Our work stresses importance selectivity successful approach signal-transduction-based antidepressants, singles out depression-relevant transducer brings proof-of-concept evidence druggability ELK-1.

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