Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery
EXPERT OPINION ON DRUG DISCOVERY(2024)
Abstract
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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Key words
DNA,deoxyribonucleic acid,nAChR neuronal nicotinic acetylcholine receptors,LGIC ligand gated ion channels,VGIC voltage gated ion channels,GPCR,G-protein coupled receptor
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