用于新药发现的牛皮癣动物模型:文献更新。

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Zih-Chan Lin, Shih-Chun Yang, Thi Thu Phuong Tran, Jia-You Fang
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引用次数: 0

摘要

银屑病是一种慢性、免疫介导的炎症性皮肤病,其发病机制涉及角化细胞增殖、免疫反应失调和血管重塑。有效治疗方法的开发主要依赖于能够重现疾病相关机制的临床前模型。涵盖领域:本综述概述了目前的体内银屑病模型,包括自发突变模型、转基因和敲除小鼠、异种移植系统、细胞因子诱导和咪喹莫德诱导模型。每个模型都被评估其复制人类牛皮癣关键组织学和免疫学特征的能力,如棘皮增生、免疫细胞浸润和细胞因子网络激活。还讨论了CRISPR/Cas9基因编辑在生成靶向模型中的应用,从而强调了其在机制研究中的潜在用途。最后,本综述还强调了银屑病在翻译适用性方面的局限性以及对多模型验证策略的需求。本文基于PubMed、Scopus和b谷歌Scholar数据库的综合文献检索,涵盖了2015年1月至2025年3月的出版物。专家意见:尽管广泛的模型开发,没有一个单一的系统完全模拟人类银屑病。咪喹莫德诱导的模型由于其实用性而被广泛使用,尽管它比慢性病理更能反映急性炎症。互补模型的结合和人源性组织或免疫成分的结合可能提高翻译相关性。基因组编辑和人性化系统的进步可能会塑造牛皮癣研究和治疗发现的未来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Animal models of psoriasis for novel drug discovery: a literature update.

Introduction: Psoriasis is a chronic, immune-mediated inflammatory skin disorder with a multifactorial pathogenesis involving keratinocyte proliferation, dysregulated immune responses, and vascular remodeling. The development of effective therapeutics mainly relies on preclinical models that can reproduce disease-relevant mechanisms.

Areas covered: This review outlines current in vivo psoriasis models, including spontaneous mutation models, transgenic and knockout mice, xenotransplantation systems, and cytokine-induced and imiquimod-induced models. Each model is evaluated for its ability to replicate key histological and immunological features of human psoriasis, such as acanthosis, immune cell infiltration, and cytokine network activation. The utility of CRISPR/Cas9 gene editing in generating targeted models is also discussed, thus highlighting its potential use for mechanistic studies. Finally, this review also emphasizes the limitations in translational applicability and the need for multimodel validation strategies regarding psoriasis. This article was based on a comprehensive literature search using PubMed, Scopus, and Google Scholar databases, covering publications from January 2015 to March 2025.

Expert opinion: Despite extensive model development, no single system fully mimics human psoriatic disease. The imiquimod-induced model remains widely used due to its practicality, although it better reflects acute inflammation compared with chronic pathology. The combination of complementary models and the incorporation of human-derived tissues or immune components may improve translational relevance. Advances in genome editing and humanized systems are likely to shape the future of psoriasis research and therapeutic discovery.

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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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