地平线上的新疗法神经科学中的靶向蛋白质降解

IF 6.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology Pub Date : 2024-09-19 DOI:10.1016/j.chembiol.2024.08.010

James A. Gregory , Christopher M. Hickey , Juan Chavez , Angela M. Cacace

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引用次数: 0

摘要

这篇微型综述探讨了蓬勃发展的靶向蛋白质降解（TPD）领域及其在神经科学和临床开发中的应用前景。靶向蛋白质降解提供了调节蛋白质水平的创新策略，是小分子药物发现和治疗干预的范式转变。重要的是，小分子蛋白质降解剂能特异性地靶向并清除中枢神经系统细胞中的致病蛋白质，而不像基因组和抗体疗法那样面临给药难题。在此，我们将回顾 TPD 技术的最新进展，重点介绍具有近端诱导降解事件驱动和迭代药理学的蛋白水解靶向嵌合体（PROTAC）蛋白降解剂分子，介绍其在神经科学研究中的应用，并讨论 TPD 转化为临床应用的巨大潜力。

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New therapies on the horizon: Targeted protein degradation in neuroscience

This minireview explores the burgeoning field of targeted protein degradation (TPD) and its promising applications in neuroscience and clinical development. TPD offers innovative strategies for modulating protein levels, presenting a paradigm shift in small-molecule drug discovery and therapeutic interventions. Importantly, small-molecule protein degraders specifically target and remove pathogenic proteins from central nervous system cells without the drug delivery challenges of genomic and antibody-based modalities. Here, we review recent advancements in TPD technologies, highlight proteolysis targeting chimera (PROTAC) protein degrader molecules with proximity-induced degradation event-driven and iterative pharmacology, provide applications in neuroscience research, and discuss the high potential for translation of TPD into clinical settings.

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来源期刊

Cell Chemical Biology Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

14.70

自引率

2.30%

发文量

143

期刊介绍： Cell Chemical Biology, a Cell Press journal established in 1994 as Chemistry & Biology, focuses on publishing crucial advances in chemical biology research with broad appeal to our diverse community, spanning basic scientists to clinicians. Pioneering investigations at the chemistry-biology interface, the journal fosters collaboration between these disciplines. We encourage submissions providing significant conceptual advancements of broad interest across chemical, biological, clinical, and related fields. Particularly sought are articles utilizing chemical tools to perturb, visualize, and measure biological systems, offering unique insights into molecular mechanisms, disease biology, and therapeutics.