Histone deacetylase inhibitors: A novel therapeutic approach for cognitive disorders

Abstract

Epigenetic mechanisms have a central role in regulating gene expression and are capable of influencing complex cognitive functions. In particular, acetylation of histone proteins is an epigenetic modification involved in mediating synaptic plasticity, learning, and memory. Emerging evidence indicates that increased histone acetylation through the inhibition of histone deacetylases (HDACs) can facilitate the formation of long-term memories in preclinical studies. Moreover, HDAC inhibitors have been reported to ameliorate cognitive deficits in animal models relevant to neurodegenerative and neurodevelopmental disorders. HDAC inhibitors have also been found to enhance the extinction of learned behaviors, including drug-seeking behaviors. Consequently, HDAC inhibition may be a useful approach in the treatment of a wide range of disorders characterized by cognitive dysfunction. Future HDAC-based pharmacotherapies will benefit from a greater understanding of different HDAC isoforms and the molecular pathways specifically involved in inducing cognitive enhancement. © Springer-Verlag Berlin Heidelberg 2011.