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离子通道与神经发育障碍

Ion Channels Involvement in Neurodevelopmental Disorders.

作者信息

D'Adamo Maria Cristina, Liantonio Antonella, Conte Elena, Pessia Mauro, Imbrici Paola

机构信息

Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Malta.

Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Italy.

出版信息

Neuroscience. 2020 Aug 1;440:337-359. doi: 10.1016/j.neuroscience.2020.05.032. Epub 2020 May 28.

Abstract

Inherited and sporadic mutations in genes encoding for brain ion channels, affecting membrane expression or biophysical properties, have been associated with neurodevelopmental disorders characterized by epilepsy, cognitive and behavioral deficits with significant phenotypic and genetic heterogeneity. Over the years, the screening of a growing number of patients and the functional characterization of newly identified mutations in ion channels genes allowed to recognize new phenotypes and to widen the clinical spectrum of known diseases. Furthermore, advancements in understanding disease pathogenesis at atomic level or using patient-derived iPSCs and animal models have been pivotal to orient therapeutic intervention and to put the basis for the development of novel pharmacological options for drug-resistant disorders. In this review we will discuss major improvements and critical issues concerning neurodevelopmental disorders caused by dysfunctions in brain sodium, potassium, calcium, chloride and ligand-gated ion channels.

摘要

编码脑离子通道的基因发生的遗传性和散发性突变,影响膜表达或生物物理特性,与以癫痫、认知和行为缺陷为特征的神经发育障碍相关,具有显著的表型和遗传异质性。多年来,对越来越多患者的筛查以及离子通道基因新发现突变的功能表征,使得能够识别新的表型并拓宽已知疾病的临床谱。此外,在原子水平上理解疾病发病机制或使用患者来源的诱导多能干细胞和动物模型方面的进展,对于指导治疗干预以及为耐药性疾病开发新的药理学选择奠定基础至关重要。在本综述中,我们将讨论由脑钠、钾、钙、氯和配体门控离子通道功能障碍引起的神经发育障碍的主要进展和关键问题。

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