Histone deacetylase in neuropathology

Abstract

Neuroepigenetics, a new branch of epigenetics, plays an important role in the regulation of gene expression. Neuroepigenetics is associated with holistic neuronal function and helps in formation and maintenance of memory and learning processes. This includes neurodevelopment and neurodegenerative defects in which histone modification enzymes appear to play a crucial role. These modifications, carried out by acetyltransferases and deacetylases, regulate biologic and cellular processes such as apoptosis and autophagy, inflammatory response, mitochondrial dysfunction, cell-cycle progression and oxidative stress. Alterations in acetylation status of histone as well as non-histone substrates lead to transcriptional deregulation. Histone deacetylase decreases acetylation status and causes transcriptional repression of regulatory genes involved in neural plasticity, synaptogenesis, synaptic and neural plasticity, cognition and memory, and neural differentiation. Transcriptional deactivation in the brain results in development of neurodevelopmental and neurodegenerative disorders. Mounting evidence implicates histone deacetylase inhibitors as potential therapeutic targets to combat neurologic disorders. Recent studies have targeted naturally-occurring biomolecules and micro-RNAs to improve cognitive defects and memory. Multi-target drug ligands targeting HDAC have been developed and used in cell-culture and animal-models of neurologic disorders to ameliorate synaptic and cognitive dysfunction. Herein, we focus on the implications of histone deacetylase enzymes in neuropathology, their regulation of brain function and plausible involvement in the pathogenesis of neurologic defects.

Keywords: Cognitive dysfunction; Epigenetics; HDAC inhibitor; Histone deacetylases; Micro RNA; Neurodevelopmental and neurodegenerative disorders; Neurogenesis; Post-transcriptional modification; Synaptic plasticity.