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.
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。
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