Histone deacetylase 3 inhibitors in learning and memory processes with special emphasis on benzamides.

ABSTRACT

Among numerous essential processes, memory and learning are important work of the brain. Epigenetic manipulations through histone acetyltransferases (HATs) and histone deacetylases (HDACs) have been implicated in memory function by modulating memory storage-related gene expression. Among these HDACs, HDAC3 is found to be important in the long-term memory process. Histone deacetylase inhibitors (HDACIs) have been established to have direct involvement to enhance the memory function through upregulation of hippocampal NR2B mRNA and phosphorylation of cyclic AMP (cAMP)-response element binding (CREB) at the NR2B gene. Though HDACIs were initially implicated as potent anticancer agents, these are also found to enhance memory or ameliorate deficits in memory dysfunction. It is done through inducing a histone hyperacetylated state. HDAC3 is a negative regulator of memory and learning and thus, deletion of HDAC3 in the dorsal hippocampus may lead to an enhanced long-term memory. Therefore, identification of potential and selective HDAC3 inhibitors may be useful in ameliorating long-term memory function and learning. In this review, detail chemico-biological and structural information of HDAC3 in memory and learning functions and benzamide-based HDAC3 inhibitors has been focussed. This may help to achieve a deep insight so that potent and selective benzamide-based HDAC3 inhibitors may be designed in future to combat memory and learning-related dysfunctions.