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.

这篇小型综述探讨了新兴的靶向蛋白降解（TPD）领域及其在神经科学和临床开发中的有前景的应用。 TPD 提供调节蛋白质水平的创新策略，呈现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专门针对并去除中枢神经系统细胞中的致病蛋白，而无需面临基因组和抗体模式的药物递送挑战。在这里，我们回顾了 TPD 技术的最新进展，重点介绍了具有邻近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) 蛋白降解分子，提供了在神经科学研究中的应用，并讨论了 TPD 转化为临床环境的巨大潜力。