GSK-3: A key regulatory target for ketamine's rapid antidepressant effects mediated by enhanced AMPA to NMDA throughput.
GSK-3: A key regulatory target for ketamine's rapid antidepressant effects mediated by enhanced AMPA to NMDA throughput.
复制标题
GSK-3：氯胺酮快速抗抑郁作用的关键调节靶点，通过增强 AMPA 到 NMDA 的吞吐量介导。
DOI：
10.1111/bdi.12452
复制
发表时间：
2016
影响因子：
5.4
通讯作者：
Machado-Vieira,Rodrigo
中科院分区：
文献类型：
--
作者：
ZarateJr,CarlosA;Machado-Vieira,Rodrigo
In the past decade, studies that provide insights into the mechanisms of action underlying ketamine’s rapid antidepressant effects have been key to identifying relevant targets for developing novel antidepressants with rapid and sustained effects1. In this context, glycogen synthase kinase 3 (GSK-3) appears to be a top candidate. GSK-3 has been extensively associated with mood disorders, particularly with regard to lithium’s effects on this target and the potential association with clinical improvement2–4. GSK-3 also plays a key role in relevant biological processes such as oxidative stress, neurogenesis, and inflammation3.In an elegant preclinical study, Beurel and colleagues5 recently demonstrated an integrated functional effect between GSK-3 and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in ketamine’s rapid antidepressant effects. Specifically, the study found that ketamine-induced GSK-3 inhibition upregulated AMPA GluA1 subunits and stabilized AMPA receptors at the cell surface. Ketamine also decreased post-synaptic density 95 (PSD-95) phosphorylation; PSD-95 is a known substrate for GSK-3 that directly regulates the number of AMPA receptors at the cell surface and, consequently, regulates synaptic strength6. Notably, the limiting effects at PSD-95 led to lower internalization of AMPA GluA1, which also had a central regulatory effect on AMPA receptor trafficking5. It is important to note that GSK-3 was previously shown to regulate AMPA receptor trafficking7 and is also associated with PSD-95 phosphorylation8. These recent findings by Beurel and colleagues underscore the relevance of GSK-3 and postsynaptic density proteins in ketamine’s rapid antidepressant effects.
登录
查看更多内容
影响因子：
3.4
作者：
de Sousa, Rafael T.;Streck, Emilio L.;Machado-Vieira, Rodrigo
通讯作者：
Machado-Vieira, Rodrigo
DOI：
10.1038/npp.2010.43
发表时间：
2010-07
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Machado-Vieira R;Manji HK;Zarate CA Jr
通讯作者：
Zarate CA Jr
影响因子：
13.5
作者：
Machado-Vieira, Rodrigo;Salvadore, Giacomo;DiazGranados, Nancy;Zarate, Carlos A., Jr.
通讯作者：
Zarate, Carlos A., Jr.
具有相似阻断动力学的低亲和力非竞争性 N-甲基-D-天冬氨酸受体拮抗剂的捕获程度差异。
影响因子：
3.5
作者：
G. A. Mealing;T. Lanthorn;C. Murray;D. Small;P. Morley
通讯作者：
P. Morley