alexa Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Genetic Syndromes & Gene Therapy

Author(s): Urdinguio RG, SanchezMut JV, Esteller M

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Abstract Epigenetic mechanisms such as DNA methylation and modifications to histone proteins regulate high-order DNA structure and gene expression. Aberrant epigenetic mechanisms are involved in the development of many diseases, including cancer. The neurological disorder most intensely studied with regard to epigenetic changes is Rett syndrome; patients with Rett syndrome have neurodevelopmental defects associated with mutations in MeCP2, which encodes the methyl CpG binding protein 2, that binds to methylated DNA. Other mental retardation disorders are also linked to the disruption of genes involved in epigenetic mechanisms; such disorders include alpha thalassaemia/mental retardation X-linked syndrome, Rubinstein-Taybi syndrome, and Coffin-Lowry syndrome. Moreover, aberrant DNA methylation and histone modification profiles of discrete DNA sequences, and those at a genome-wide level, have just begun to be described for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, and in other neurological disorders such as multiple sclerosis, epilepsy, and amyotrophic lateral sclerosis. In this Review, we describe epigenetic changes present in neurological diseases and discuss the therapeutic potential of epigenetic drugs, such as histone deacetylase inhibitors. This article was published in Lancet Neurol and referenced in Journal of Genetic Syndromes & Gene Therapy

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