期刊
ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE
卷 42, 期 2, 页码 156-164出版社
MASSON EDITEUR
DOI: 10.1016/j.encep.2016.02.003
关键词
GSK-3; Treatment-resistant depression; Ketamine; Lithium
资金
- Servier
Background. - Since the discovery of antidepressants, new treatments have emerged with fewer side effects but no greater efficacy. Glycogen synthase kinase 3 beta (GSK-3 beta), a kinase known for its activity on glycogen synthesis, has in the last few years raised growing interest in biological psychiatry. Several efficient treatments in major depression have an inhibitory effect on this kinase, which could be targeted in new mood disorder treatments. Methods. - The aim of this review is to summarize findings concerning the intracellular pharmacologic effects of GSK-3 beta inhibitors on mood. After a brief description of the intracellular transduction pathways implicated in both GSK-3 beta and mood disorders, we reviewed the results demonstrating GSK-3 beta involvement in the effects of lithium and ketamine. Results. - GSK-3 beta can be inhibited through several mechanisms such as serine phosphorylation or binding in a proteic scaffold and others. Its inhibition is implicated in numerous cellular pathways of interest involved in neuronal growth and architecture, cell survival, neurogenesis or synaptic plasticity. This inhibition appears to be both efficient and sufficient in improving mood in animal models. In human beings, several levels of evidence show GSK-3 beta inhibition with antidepressant use. Crucially, strong inhibition has been shown with lithium via the proteic scaffold PP2A/beta-arrestin/AKT, and with the rapid antidepressant effect of ketamine via p70S6K. Conclusion. - Our review focuses on mechanisms whereby the GSK-3 beta pathway has a part in the antidepressant effect of lithium and ketamine. This article highlights the importance of translational research from cell and animal models to the clinical setting in order to develop innovative therapeutic targets. (C) L'Encephale, Paris, 2016.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据