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Model of the Htt—REST—miR-137 regulatory circuit in HD. In healthy individuals, wild-type Htt sequesters REST in the cytoplasm, thereby allowing higher levels of miR-137 expression, which leads to the suppression of Htt translation. In HD, mutant Htt loses its ability to inhibit the nuclear transfer of REST. REST represses the transcription of the MIR137 gene, which results in lower miR-137 levels and consequent increase in the translation of the mutant Htt protein.
