Polyglutamine Aggregation Inhibitor III, C2-8 is a cell-permeable amidosulfonamide compound that potently inhibits polyglutamine (polyQ)-aggregation in Huntington's disease (HD); CA1 neuronal hippocampal slices in the range of 0.1 μM - 10 μM, and Htt-103Q-EGFP PC12 cells with an IC50 of 50 nM. Furthermore, Polyglutamine Aggregation Inhibitor III, C2-8 relieves the progressive neurodegeneration in Drosophila expressing Httex1 93QP in a dose-dependent fashion.