Hohman Grace, Watson Ava, Eldeeb Mohamed A
Department of Chemistry, Illinois State University, Normal, IL 61761, USA.
Biology (Basel). 2025 Apr 14;14(4):420. doi: 10.3390/biology14040420.
Proper cellular function hinges on appropriate subcellular protein localization. When cellular proteins become mislocalized, they can accumulate, cause cellular damage, and disrupt many biochemical and cellular processes. Notably, mislocalized protein accumulation and the resulting cytotoxic effects are salient features of neurodegenerative diseases including Alzheimer's, Parkinson's disease, and ALS. The detrimental cellular consequences of mislocalized proteins accumulation make it crucial to develop techniques and approaches that counteract this malfunction. Remarkably, a recent study by Ng et al. introduced targeted relocalization-activating molecules (TRAMs) as a novel molecular tool for relocalizing endogenous target proteins to counteract disease-associated mislocalized proteins. The authors developed a quantitative single-cell analysis to evaluate the strength and relocalization capability of TRAMs by coupling a target protein and a shuttle protein. Herein, we briefly highlight and discuss the potential molecular implications for targeted protein relocalization as an effective approach for correcting mislocalized proteins.
正常的细胞功能取决于适当的亚细胞蛋白质定位。当细胞蛋白质发生错误定位时，它们会积累，导致细胞损伤，并扰乱许多生化和细胞过程。值得注意的是，错误定位的蛋白质积累以及由此产生的细胞毒性作用是包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症在内的神经退行性疾病的显著特征。错误定位的蛋白质积累对细胞产生的有害后果使得开发能够对抗这种功能故障的技术和方法至关重要。值得注意的是，Ng等人最近的一项研究引入了靶向重新定位激活分子（TRAM），作为一种将内源性靶蛋白重新定位以对抗与疾病相关的错误定位蛋白的新型分子工具。作者开发了一种定量单细胞分析方法，通过将靶蛋白和穿梭蛋白偶联来评估TRAM的强度和重新定位能力。在此，我们简要强调并讨论靶向蛋白质重新定位作为纠正错误定位蛋白质的有效方法的潜在分子意义。
