IDB decreases uN2CpolyG aggregation in cells and restores motor performance, lifespan, and ATP synthesis in uN2CpolyG-GFP–expressing flies. (A) IDB treatments at concentrations of 0, 1, 2, 3, and 4 μM were applied to cells expressing uN2CpolyG. Representative immunofluorescence images showed 2 μM IDB decreased uN2CpolyG aggregate formation in SH-SY5Y cells. (B) The proportion of the uN2CpolyG aggregates at different IDB concentrations. The concentration of 2 μM IDB significantly decreased the number of aggregates. (C) Flies expressing uN2CpolyG were fed with 0, 7, 15, and 50 μM IDB. The locomotor index was measured in adult flies at different ages. IDB treatment significantly restored motor performance of flies expressing uN2CpolyG at day 20 and day 35. (D) Effect of IDB on the lifespan of uN2CpolyG-expressing flies. 15 μM IDB treatment significantly improved the survival rate of flies expressing uN2CpolyG. The median lifespan was 35, 30, 55, and 35 d for flies treated at concentrations of 0, 7, 15, and 50 μM IDB, respectively. (log-rank Mantel-Cox test; n = 233–279/genotype for flies; **P < 0.01, ***P < 0.001, ****P < 0.0001). (E) IDB significantly improved ATP levels in flies expressing uN2CpolyG protein. Fly genotype: Actin-Gal4 > UAS-uN2CpolyG-GFP. Error bars correspond to the SEM.