Synaptic Wnt signaling-a contributor to major psychiatric disorders?
Synaptic Wnt signaling-a contributor to major psychiatric disorders?
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DOI：
10.1007/s11689-011-9083-6
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发表时间：
2011-06
影响因子：
4.9
通讯作者：
Cheyette, Benjamin N. R.
中科院分区：
文献类型：
--
作者：
Okerlund, Nathan D.;Cheyette, Benjamin N. R.
WNT信号是帮助组织神经系统发育的关键途径。它影响发育中的神经系统中的细胞增殖、细胞命运和细胞迁移，以及轴突引导、树突发育和突触形成。鉴于这种广泛的作用，Wnt信号的失调可能会对神经发育产生许多有害的影响，从而在许多不同的方式中促进神经发育障碍的发病。一些主要的精神障碍，包括精神分裂症、双相情感障碍和自闭症谱系障碍，逐渐被理解为神经系统发育的微妙失调，特别是突触的形成和维护。因此，这篇综述将涉及Wnt信号对神经发育的重要性，同时专注于积累Wnt信号在突触作用方面的证据。这些观察将在目前对主要精神疾病、聚光性精神分裂症、双相情感障碍和自闭症谱系障碍的神经发育基础的理解的背景下进行讨论。总之，本综述将集中于突触形成和维持在主要精神疾病中的潜在作用，并总结Wnt信号缺陷可能通过影响这些晚期神经分化过程而参与其发病机制的证据。
Wnt signaling is a key pathway that helps organize development of the nervous system. It influences cell proliferation, cell fate, and cell migration in the developing nervous system, as well as axon guidance, dendrite development, and synapse formation. Given this wide range of roles, dysregulation of Wnt signaling could have any number of deleterious effects on neural development and thereby contribute in many different ways to the pathogenesis of neurodevelopmental disorders. Some major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders, are coming to be understood as subtle dysregulations of nervous system development, particularly of synapse formation and maintenance. This review will therefore touch on the importance of Wnt signaling to neurodevelopment generally, while focusing on accumulating evidence for a synaptic role of Wnt signaling. These observations will be discussed in the context of current understanding of the neurodevelopmental bases of major psychiatric diseases, spotlighting schizophrenia, bipolar disorder, and autism spectrum disorder. In short, this review will focus on the potential role of synapse formation and maintenance in major psychiatric disorders and summarize evidence that defective Wnt signaling could contribute to their pathogenesis via effects on these late neural differentiation processes.
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