[EPIGENETIC ENZYMES AS THERAPEUTIC TARGETS FOR TREATING BRAIN DISORDERS]

At present, epigenetic regulation is considered as a dynamic mechanism by means of which cells realize adaptive response to signals from both the inner medium and environment. DNA methylation, as bidirectional balance of the activity of histone-acetylation and -deacetylation (HDAC) enzymes, determines the conformation of chromatin thus playing the main role in "appropriate" gene expression. HDACs represent emerging therapeutic targets in the context of treating various forms of neurological and mental illness. A wide range of brain diseases are associated with imbalance between protein acetylation levels and tran- scriptional dysfunctions. Increasing evidence supports the notion that histone hypoacetylation and transcriptional dysfunction are involved in a large number of neurodegenerative conditions in vivo and in vitro. Histone deacetylase inhibitors (HDACIs) that affect the acetylation status of histones and other important cellular proteins--have been recognized as potentially useful therapeutic means for a broad range of human disorders. This review summarizes the current state of development of HDACIs based therapeutics and their application for the treatment of human brain neurodegenerative, ischemic, and cognitive pathologies. Treatment with various HDACIs can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention based on the experimental search and clinical testing of HDACIs representing compounds of various classes.