Reference: Taylor JP and Fischbeck KH (2002) Altered acetylation in polyglutamine disease: an opportunity for therapeutic intervention? Trends Mol Med 8(5):195-7

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Abstract


Recent investigations into polyglutamine diseases suggest that aberrant transcriptional regulation might be central to the molecular pathogenesis, perhaps because of inappropriate interaction between mutant proteins and important nuclear factors. Several groups have reported an interaction of mutant polyglutamine with histone acetylases, implicating defective acetylation as a cause of abnormal transcription. An important recent observation is that reversal of the acetylation defect with histone deacetylase inhibitors ameliorates polyglutamine toxicity in yeast, mammalian cell culture, and animal models. These encouraging findings suggest that a novel strategy--pharmacological restoration of histone acetylation-- could prove effective in treating this group of devastating illnesses.

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Taylor JP, Fischbeck KH
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