利用爪蟾卵母细胞模拟神经疾病以发现新药的进展。

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI:10.1080/17460441.2023.2270902
Eoin C O'Connor, Kumiko Kambara, Daniel Bertrand
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引用次数: 0

摘要

简介:引进非洲爪蟾卵母细胞模型约50年前,用于表达重组蛋白已获得广泛的应用。本文作者综述了使用该模型系统带来的好处,重点是对神经疾病机制进行建模并应用于药物发现。涵盖的领域:本综述使用了从配体门控离子通道到转运蛋白的多个例子,根据最新的出版物,介绍了使用非洲爪蟾卵母细胞所带来的好处。研究范围从基因突变的表征到发现中枢神经系统疾病的新治疗方法。专家意见:针对中枢神经系统障碍的新药开发在从临床前研究到临床研究的转化过程中失败。随着遗传学和分子生物学的进步凸显了由单个到几个氨基酸交换引起的巨大功能差异,对针对人类蛋白质的药物筛选和功能测试的需求正在增加。利用非洲爪蟾卵母细胞对临床相关遗传变异进行精确建模和表征,构成了一个强大的模型系统,可用于为中枢神经系统药物发现和开发的各个方面提供信息。
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Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery.

Introduction: Introduced about 50 years ago, the model of Xenopus oocytes for the expression of recombinant proteins has gained a broad spectrum of applications. The authors herein review the benefits brought from using this model system, with a focus on modeling neurological disease mechanisms and application to drug discovery.

Areas covered: Using multiple examples spanning from ligand gated ion channels to transporters, this review presents, in the light of the latest publications, the benefits offered from using Xenopus oocytes. Studies range from the characterization of gene mutations to the discovery of novel treatments for disorders of the central nervous system (CNS).

Expert opinion: Development of new drugs targeting CNS disorders has been marked by failures in the translation from preclinical to clinical studies. As progress in genetics and molecular biology highlights large functional differences arising from a single to a few amino acid exchanges, the need for drug screening and functional testing against human proteins is increasing. The use of Xenopus oocytes to enable precise modeling and characterization of clinically relevant genetic variants constitutes a powerful model system that can be used to inform various aspects of CNS drug discovery and development.

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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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