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Wnt 与锂:神经系统疾病治疗中的共同命运?

Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

机构信息

UMR 8194 CNRS, University Paris Descartes, 45 rue des Saints-Pères, 75270, Paris Cedex 6, France.

出版信息

Cell Mol Life Sci. 2014 Apr;71(7):1123-48. doi: 10.1007/s00018-013-1378-1. Epub 2013 Jun 9.

Abstract

Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.

摘要

Wnt 信号通路对于神经发生、神经祖细胞的命运、发育过程中神经元回路的形成、神经元定位和极化、轴突和树突发育以及最后突触发生都是必需的。这条信号通路也与神经胶质细胞的产生和分化有关。在这篇综述中,我们描述了 Wnt 信号通路的作用机制及其在神经系统发育和正常功能中的作用。我们还说明了失调的 Wnt 通路如何导致精神疾病、神经退行性疾病和脱髓鞘疾病。用于治疗双相情感障碍的锂抑制了 GSK3β,这是 Wnt/β-catenin 通路的一个核心酶。因此,锂在某种程度上可以模拟 Wnt 通路。我们强调了锂治疗与 Wnt 通路调节之间的可能对话,以治疗神经系统疾病。

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