DNA (cytosine-5) methyltransferase inhibitors: a potential therapeutic agent for schizophrenia.

MOL 33266 1 DNA ( cytosine - 5 ) Methyltransferase Inhibitors : A Potential Therapeutic for Schizophrenia

The reelin and GAD67 promoters are activated by epigenetic drugs that facilitate the disruption of local repressor complexes.

The epigenetic down-regulation of genes is emerging as a possible underlying mechanism of the GABAergic neuron dysfunction in schizophrenia. For example, evidence has been presented to show that the promoters associated with reelin and GAD67 are down-regulated as a consequence of DNA methyltransferase (DNMT)-mediated hypermethylation. Using neuronal progenitor cells to study this regulation, we...

DNA methyltransferase inhibitors-state of the art.

BACKGROUND DNA methylation is the addition of a methyl group to the 5 position of cytosine. It is an epigenetic process with several effects, including chromatin structure modulation, transcriptional repression and the suppression of transposable elements. In malignancy, methylation patterns change, resulting in global hypomethylation with regional hypermethylation. This can lead to genetic ins...

Methylation inhibitors can increase the rate of cytosine deamination by (cytosine-5)-DNA methyltransferase.

The target cytosines of (cytosine-5)-DNA methyltransferases in prokaryotic and eukaryotic DNA show increased rates of C-->T transition mutations compared to non-target cytosines. These mutations are induced either by the spontaneous deamination of 5-mC-->T generating inefficiently repaired G:T rather than G:U mismatches, or by the enzyme-induced C-->U deamination which occurs under conditions o...

Human Cancer Biology MDM2 Overexpression Deregulates the Transcriptional Control of RB/E2F Leading to DNA Methyltransferase 3A Overexpression in Lung Cancer

Purpose: Overexpression of DNA 50-cytosine-methyltransferase 3A (DNMT3A), which silences genes including tumor suppressor genes (TSG), is involved inmany cancers. Therefore, we examined whether the transcriptional deregulation of RB/MDM2 pathway was responsible for DNMT3A overexpression and analyzed the therapeutic potential of MDM2 antagonist for reversing aberrant DNA methylation status in