DNA (cytosine-5) methyltransferase inhibitors: a potential therapeutic agent for schizophrenia.
In this issue of Molecular Pharmacology, Kundakovic et al. (p. 644) present compelling evidence suggesting that the promoters for reelin and GAD67 are coordinately regulated. The regulation occurs at the level of DNA (cytosine-5) methylation. Moreover, the authors present evidence suggesting that pharmacologic inhibition of DNA methyltransferase results in reversal of methylation, loss of methyl-DNA binding proteins and relief of repression. Repression of both reelin and GAD67 has been implicated in the pathogenesis of schizophrenia. Therefore, these results suggest that the reelin and GAD67 promoters are subject to continuous repression by DNA methyltransferase and that inhibitors of DNA methyltransferase represent a potential treatment for Schizophrenia.
Levenson
Jonathan M
JM
Department of Pharmacology and The Waisman Center, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA. jlevenson@wisc.edu
D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D019175:DNA Methylation; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000091042:Reelin Protein; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics*
D015816:Cell Adhesion Molecules, Neuronal; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D004317:Doxorubicin; D004248:DNA (Cytosine-5-)-Methyltransferases; C000717127:RELN protein, human; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1