TAR DNA binding protein 43 (TDP-43) is a key target in amyotrophic lateral sclerosis (ALS) treatment. Here, based on hydrophobic tagging strategy, we designed and synthesized a series of single or double hydrophobic tags conjugated peptides D1-D8. Among them, it was found that D4 displayed strongest ability to induce TDP-43 degradation in cells. D4 could reduce TDP-43 induced cytotoxicity. Besides, D4 could reduce TDP-43 levels in a transgenic drosophila model.

中文翻译：

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T-43特异性还原由Di-疏水标签偶联的肽诱导。

TAR DNA结合蛋白43（TDP-43）是肌萎缩性侧索硬化症（ALS）治疗的关键靶标。在这里，基于疏水标记策略，我们设计和合成了一系列的单或双疏水标签结合肽D1-D8。其中，发现D4显示出最强的诱导细胞中TDP-43降解的能力。D4可以降低TDP-43诱导的细胞毒性。此外，D4可以降低转基因果蝇模型中的TDP-43水平。