CRISPR screens for the discovery of novel ferroptosis targets: progress and perspectives.

IF 6.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2026-09-02 DOI:10.1016/j.bcp.2026.118410

Weibang Yu, Yiwen Cui, Qi Zhao, Lianxiang Luo

引用次数: 0

Abstract

Ferroptosis is a distinct, iron-dependent form of regulated cell death characterized by lipid peroxidation. Despite its growing significance in physiology and disease, the molecular networks that govern ferroptosis are not yet fully understood. Genome-wide CRISPR screens have broadened the regulatory landscape of ferroptosis by revealing both conserved and context-dependent mechanisms. In this review, we summarize recent advances in CRISPR-based ferroptosis screens, highlighting a transition from in vitro CRISPR screens to in vivo platforms and single-cell CRISPR screens. We also discuss the potential translation of key targets, focusing on their structural druggability and therapeutic potential. By outlining objective-driven screening strategies, this review seeks to provide options for exploring the distinct mechanisms of ferroptosis and to accelerate its translation into therapeutic opportunities for various diseases.

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CRISPR筛选发现新的铁下垂靶点：进展和前景。

铁下垂是一种独特的，铁依赖形式的调节细胞死亡的特点是脂质过氧化。尽管其在生理和疾病中的重要性日益增加，但控制铁下垂的分子网络尚未完全了解。全基因组CRISPR筛选通过揭示保守和环境依赖的机制，扩大了铁死亡的调控范围。在这篇综述中，我们总结了基于CRISPR的铁垂症筛选的最新进展，强调了从体外CRISPR筛选到体内平台和单细胞CRISPR筛选的转变。我们还讨论了关键靶点的潜在翻译，重点是它们的结构药物性和治疗潜力。通过概述目标驱动的筛选策略，本综述旨在为探索铁下垂的不同机制提供选择，并加速其转化为各种疾病的治疗机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.