Neuroplasticity signaling pathways linked to the pathophysiology of schizophrenia.

Neuroplasticity signaling pathways linked to the pathophysiology of schizophrenia.
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DOI:
10.1016/j.neubiorev.2010.10.005
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发表时间:
2011-01
影响因子:
8.2
通讯作者:
Coyle, Joseph T.
Coyle, Joseph T.
中科院分区:
医学1区
文献类型:
--
作者:
Balu, Darrick T.;Coyle, Joseph T.

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精神分裂症是一种严重的精神疾病,困扰着世界上近1%的人口。精神分裂症的主要病理特征之一是突触连接的紊乱。虽然精神分裂症的病因尚不清楚,但它似乎是一种发育障碍,涉及大量潜在的危险基因的相互作用,除了罕见的、高度渗透的拷贝数变异外,没有一个基因会产生强烈的影响。本综述的目的是详细介绍可能的精神分裂症危险基因(Disk-1、neuRegin/ErbB4、dybindin、Akt1、BDNF和NMDA受体)如何参与调节神经可塑性,以及它们的表达变化如何导致精神分裂症的连接中断。此外,这篇综述还强调了这些风险基因中有多少聚集在一起来调节共同的神经递质系统和信号通路。未来旨在阐明这些危险基因功能的研究将为精神分裂症的病理生理学提供新的见解,并可能导致提名新的治疗靶点,以恢复精神分裂症和相关疾病大脑中适当的突触连接。
Schizophrenia is a severe mental illness that afflicts nearly 1% of the world's population. One of the cardinal pathological features of schizophrenia is perturbation in synaptic connectivity. Although the etiology of schizophrenia is unknown, it appears to be a developmental disorder involving the interaction of a potentially large number of risk genes, with no one gene producing a strong effect except rare, highly penetrant copy number variants. The purpose of this review is to detail how putative schizophrenia risk genes (DISC-1, neuregulin/ErbB4, dysbindin, Akt1, BDNF, and NMDA receptor) are involved in regulating neuroplasticity and how alterations in their expression may contribute to the disconnectivity observed in schizophrenia. Moreover, this review highlights how many of these risk genes converge to regulate common neurotransmitter systems and signaling pathways. Future studies aimed at elucidating the functions of these risk genes will provide new insights into the pathophysiology of schizophrenia and will likely lead to the nomination of novel therapeutic targets for restoring proper synaptic connectivity in the brain in schizophrenia and related disorders.
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