Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action.
Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action.
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DOI：
10.1176/appi.ajp.2009.08121873
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Javitch JA
中科院分区：
文献类型：
--
作者：
Freyberg Z;Ferrando SJ;Javitch JA
多巴胺D2受体拮抗剂是临床使用的所有抗精神病药物的统一性质。值得注意的是，这些药物发挥作用的效应分子仍然缺乏特征。Akt/糖原合成酶激酶-3（GSK-3）和无翅（Wnt）信号通路在许多遗传学和死后研究中与精神分裂症相关，这两条通路正受到越来越多的关注。抗精神病药物可以治疗精神病症状，至少部分是通过调节Akt、GSK-3和Wnt相关细胞内信号传导的水平和活性。作者回顾了Akt/GSK-3和Wnt相关通路参与精神分裂症发病机制的证据，以及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精神分裂症相关疾病的替代疗法。
Dopamine D2 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.
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DOI：
10.1017/s1461145704004535
发表时间：
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影响因子：
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