The study investigates the role of histone deacetylase (HDAC) inhibitors in arresting polyglutamine-dependent neurodegeneration in Drosophila. The research focuses on the interaction between huntingtin (Htt) exon 1 protein (Httex1p) and acetyltransferase domains of proteins like CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). Httex1p interacts with these proteins, inhibiting their acetyltransferase activity and reducing histone H3 and H4 acetylation levels in cultured cells. In vivo, HDAC inhibitors prevent progressive neuronal degeneration and reduce lethality in Drosophila models of polyglutamine diseases. These findings suggest that HDAC inhibitors may be effective in slowing or preventing neurodegeneration in Huntington's disease and other polyglutamine-repeat diseases, even after symptom onset. The study also explores the biochemical basis of these interactions and the importance of acetylation levels in polyglutamine pathogenesis.The study investigates the role of histone deacetylase (HDAC) inhibitors in arresting polyglutamine-dependent neurodegeneration in Drosophila. The research focuses on the interaction between huntingtin (Htt) exon 1 protein (Httex1p) and acetyltransferase domains of proteins like CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). Httex1p interacts with these proteins, inhibiting their acetyltransferase activity and reducing histone H3 and H4 acetylation levels in cultured cells. In vivo, HDAC inhibitors prevent progressive neuronal degeneration and reduce lethality in Drosophila models of polyglutamine diseases. These findings suggest that HDAC inhibitors may be effective in slowing or preventing neurodegeneration in Huntington's disease and other polyglutamine-repeat diseases, even after symptom onset. The study also explores the biochemical basis of these interactions and the importance of acetylation levels in polyglutamine pathogenesis.