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 dis-orders 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 transcrip-tion. 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, indicat-ing that both genetic and epigenetic information are indispensable. The epigenetic regu-latory mechanisms in the central nervous system have recently been object of intense re-search. As a result, mutations of epigenetic modulator genes have been implicated in sev-eral neurodegenerative and psychiatric disorders. This article reviews some common dis-orders, 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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