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精神分裂症中选择性前体 mRNA 剪接的异常调控。

Aberrant regulation of alternative pre-mRNA splicing in schizophrenia.

机构信息

Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.

出版信息

Neurochem Int. 2010 Dec;57(7):691-704. doi: 10.1016/j.neuint.2010.08.012. Epub 2010 Sep 9.

Abstract

Alternative pre-mRNA splicing plays a key role in the control of gene expression in both neurons and glial cells, and failure or dysregulation of these splicing events can cause developmental abnormalities and lead to the development of pathology. Schizophrenia is a common mental disorder that presents as a complex condition. Many factors, of genetic, epigenetic and environmental etiology, such as developmental abnormalities in myelination, synapses and neurotransmission, have been implicated in this disorder. Intriguingly, aberrant alternative splicing of genes related to neurodevelopment and neural function has been detected in schizophrenia and related disorders. In this review, we discuss the aberrant splicing of specific genes for each candidate cause of schizophrenia. Finally, we discuss the only example that has been researched in detail, from the cause to clarification of the mechanism, in ongoing studies into the associations between brain disorders and abnormal splicing.

摘要

可变剪接在神经元和神经胶质细胞的基因表达调控中起着关键作用,这些剪接事件的失败或失调可导致发育异常,并导致病理学的发生。精神分裂症是一种常见的精神障碍,表现为一种复杂的病症。许多因素,包括遗传、表观遗传和环境病因,如髓鞘、突触和神经递质的发育异常,都与这种疾病有关。有趣的是,在精神分裂症和相关疾病中已经检测到与神经发育和神经功能相关的基因的异常可变剪接。在这篇综述中,我们讨论了每个候选精神分裂症病因的特定基因的异常剪接。最后,我们讨论了唯一一个在正在进行的脑疾病和异常剪接之间关联研究中被详细研究的例子,从原因到机制的阐明。

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