TDP-43 specific reduction induced by Di-hydrophobic tags conjugated peptides.

•D4 contained three parts: a hydrophobic motif, a TDP-43 recognition motif and a cell-penetrating peptide.•D4 displayed the strongest ability to induce the degradation of intracellular TDP-43.•D4 could reduce the cytotoxicity induced by overexpression of TDP-43.•D4 could down-regulate the TDP-43 level in TDP-43 overexpressed Drosophila.