ABSTRACT
Epigenetics, heritable changes in gene expression that do not involve changes in DNA sequence, is known to be involved in disease. Two important epigenetic changes that are known to contribute to disease are abnormal methylation patterns of DNA and modifications of histones in chromatin. This review describes a new development in pharmacology, epigenetic therapy, which attempts to correct these changes. At present two groups of drugs are being developed. One inhibits DNA methyltransferases (DNMTs) resulting in the inhibition of DNA methylation. This group of drugs may prove to be useful in the treatment of cancer where hypermethylation of tumour suppressor genes is known to lead to silencing of these genes. The other group of drugs inhibits histone deacetylases (HDACs) resulting in the accumulation of acetylated histones which are thought to mediate the anticancer effects of these drugs. Both these drug groups have shown promising results in drug trials for the treatment of cancer. Since epigenetic changes are thought to underlie a wide range of diseases, the scope of epigenetic therapy is likely to expand.
Subject(s)
Clinical Trials as Topic , DNA Methylation , DNA Modification Methylases/antagonists & inhibitors , Drug Design , Drug Synergism , Enzyme Inhibitors/classification , Epigenesis, Genetic , Histone Deacetylases/antagonists & inhibitors , Histones/metabolism , Humans , Molecular Biology , Oligonucleotides, Antisense/therapeutic useABSTRACT
Las Glutatión S-transferasas (GST) de organismos no-vertebrados no han sido estudiadas con la misma intensidad que las de mamíferos. El interés en las GST en no-vertebrados radica en su importancia como protección bioquímica de los organismos expuestos a compuestos químicos ambientales. En efecto, se ha observado que niveles elevados de GST podrían estar asociados con la tolerancia a pesticidas. La intención de esta actualización es revisar el nivel de conocimiento actual sobre estas enzimas en no-vertebrados, comparándolas con las de mamíferos. Evaluar la contribución de estos estudios al conocimiento del rol de las glutinatión transferasas en general, e intentar discernir la dirección de las futuras investigaciones en este campo