TARGETING EPIGENETICS TO ACHIEVE THERAPEUTIC SELECTIVITY IN DISORDERS OF THE CENTRAL NERVOUS SYSTEM
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Targeting epigenetics may offer the potential for achieving therapeutic selectivity in disorders of the central nervous system, by simultaneously modulating the expression of multiple genes involved in disease mechanisms. Histone acetylation, regulated by histone acetyltransferases and deacetylases, affects chromatin condensation and gene transcription. DNA methylation is also involved in histone modification. Methylation of CpG islands in promoter regions is associated with gene silencing. The development and functions of the human central nervous system are largely shaped by postnatal experiences, indicating that both genetic and epigenetic information are indispensable. The epigenetic regulatory mechanisms in the central nervous system have recently been object of intense research. As a result, mutations of epigenetic modulator genes have been implicated in several neurodegenerative and psychiatric disorders. This article reviews some common disorders, such as Alzheimer's disease, mood disorders and Attention Deficit Hyperactivity Disorder, where epigenetic mechanisms may offer potential targets for experimental therapeutics.
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