Unique functional roles for class I and class II histone deacetylases in central nervous system development and function

Non-specific pharmacological inhibition of the histone deacetylase (HDAC) family of enzymes has largely beneficial effects in a variety of diverse contexts including cancer, cognitive function, and neurodegeneration. This review will discuss the role of individual HDAC isoforms in brain function during development and in the adult. Importantly class I and class II HDACs exhibit distinct cellular and subcellular expression patterns and utilize different signaling pathways to influence their substrates. Moreover, dissociable phenotypic outcomes emerge following manipulation of individual HDACs in the brain. To date, pharmacological inhibitors capable of targeting individual HDACs have proven difficult to develop, an obstacle that must be overcome to unlock the substantial clinical promise of manipulating endogenous HDAC isoforms in the central nervous system.

► Conditional knockout strategies are elucidating the role of individual HDACs.
► Class I vs. Class II HDACs have distinct roles in development and adult behavior.
► Potential clinical avenues for isoform-specific HDAC inhibition are discussed.