Histone deacetylase class II and acetylated core histone immunohistochemistry in human brains with Huntington’s disease

Background and objectiveHuntington’s disease (HD) is an autosomal dominant neurodegenerative disorder, caused by a CAG/polyglutamine repeat expansion, which is associated with a dysregulation of histone function and an impairment of protein transcription. Histone deacetylase (HDAC) inhibitors, such as vorinostat (SAHA), have shown promise as therapeutic agents. However, there have been few studies on the expression of HDACs and acetylated core histones (AcHs) in either normal animals or humans, or in HD patients or HD animal models. Therefore, we investigated the expression of HDACs and AcHs in HD brain by immunohistochemistry, and have compared findings with elderly control subjects and patients with frontotemporal lobar degeneration (FTLD) to determine whether any observed changes were specific for HD. Results and conclusion: we show specific and significant losses of AcH2A, AcH2B, AcH3 and AcH4 expression from cells in the caudate nucleus and Purkinje cells of the cerebellum in HD compared to patients with FTLD and control subjects, while the level of HDAC 5 was increased in these cells.

► Increase in HDAC 5 levels in caudate nucleus and Purkinje cells HD.
► Loss of histone acetylation from caudate nucleus and Purkinje cells in HD.
► The preservation of HDAC 5 provides a valid target for therapy with suitable HDAC inhibitors.