Targeting the correct HDAC(s) to treat cognitive disorders.

Changes in gene expression in the brain may underlie cognitive deficits inherent to normal aging and neurodegenerative disease. However, the mechanisms underlying pathological alterations in the brain transcriptome are incompletely understood. Epigenetic mechanisms such as DNA methylation and histone acetylation have been shown to be important for memory processes in the adult brain. There is accumulating evidence that altered chromatin plasticity and histone acetylation are also involved in cognitive aging, neurodegeneration, and neuropsychiatric diseases. Inhibitors of histone deacetylase (HDAC) exhibit neuroprotective and neuroregenerative properties in animal models of various brain diseases. As such, targeting of HDACs seems to be a promising therapeutic strategy. In this review, we discuss the specific roles of each HDAC protein and the possible function of distinct histone modifications. We hope that this knowledge will aid in the development of diagnostic tools and in designing more potent and specific treatment for neurological disorders targeting selective HDAC proteins.