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Regulation of the postnatal development of dopamine neurons of the substantia nigra in vivo by Akt/protein kinase B.Akt/蛋白激酶B对体内黑质多巴胺能神经元产后发育的调节作用
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Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival.氧化应激和线粒体功能障碍作为缺血性神经元死亡和存活的决定因素。
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Insulin-modulated Akt subcellular localization determines Akt isoform-specific signaling.胰岛素调节的Akt亚细胞定位决定Akt亚型特异性信号传导。
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Arrestin3 mediates D(2) dopamine receptor internalization.抑制蛋白3介导D2多巴胺受体内化。
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Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling.精神分裂症相关基因1通过调节糖原合成酶激酶3β/β-连环蛋白信号通路调控神经祖细胞增殖。
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PI3K/Akt: getting it right matters.磷脂酰肌醇-3激酶/蛋白激酶B信号通路：正确理解至关重要。
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Role of the phosphoinositide 3-kinase-Akt-mammalian target of the rapamycin signaling pathway in long-term potentiation and trace fear conditioning memory in rat medial prefrontal cortex.磷酸肌醇3激酶-Akt-雷帕霉素哺乳动物靶点信号通路在大鼠内侧前额叶皮质长时程增强和痕迹恐惧条件记忆中的作用
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9
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10
Association study of Wnt signaling pathway genes in bipolar disorder.双相情感障碍中Wnt信号通路基因的关联研究
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Akt/GSK-3 和 Wnt 信号通路在精神分裂症和抗精神病药物作用中的作用。

Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action.

机构信息

Department of Psychiatry, Center for Molecular Recognition, College of Physicians and Surgeons, Columbia University, NY 10032, USA.

出版信息

Am J Psychiatry. 2010 Apr;167(4):388-96. doi: 10.1176/appi.ajp.2009.08121873. Epub 2009 Nov 16.

DOI:10.1176/appi.ajp.2009.08121873
PMID:19917593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3245866/
Abstract

Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders.

摘要

多巴胺 D2 受体拮抗作用是所有临床应用的抗精神病药物的共同特性。值得注意的是，这些药物发挥作用的效应分子仍未得到很好的描述。越来越多的注意力集中在 Akt/糖原合成激酶-3 (GSK-3) 和 Wnt 信号通路，这些通路在许多遗传和尸检研究中与精神分裂症有关。抗精神病药物可能通过调节 Akt、GSK-3 和 Wnt 相关细胞内信号的水平和活性来治疗精神病症状，至少在一定程度上是这样。作者回顾了 Akt/GSK-3 和 Wnt 相关途径参与精神分裂症发病机制的证据，以及由典型和非典型抗精神病药物介导的与这些分子相关的细胞内事件的细节。对 Akt/GSK-3 和 Wnt 信号的进一步研究可能最终导致与精神分裂症相关疾病的替代治疗方法。