Histone deacetylase 4 promotes cytoplasmic huntingtin aggregation in mouse models of Huntington disease

In the brains of mice with Huntington disease (HD), the transcriptional repressor histone deacetylase 4 (HDAC4) colocalizes with mutant huntingtin to form cytoplasmic inclusions, according to research reported in PLoS Biology. Mielcarek et al. found that an HDAC4 knock-down in these animals delayed the formation of these inclusions without affecting global transcriptional regulation or nuclear huntingtin aggregation. The knock-down also restored neuronal and synaptic function, ameliorated neurological impairments, and increased survival times. The researchers conclude that HDAC4 could represent a new target for small-molecule therapeutics in HD.