Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease

ABSTRACT: Huntington Disease (HD) is a dominantly inherited, relentlessly progressive neurodegenerative disease. Caused by a polyglutamine expansion in the mutant huntingtin protein (mhtt), HD pathogenesis impairs function in the cerebral cortex and in medium spiny neurons of the striatum and involves transcriptional dysregulation of a number of genes. Of these genes, silencing of genes related to mitochondrial function is believed to explain metabolic dysfunction in rodent models of HD. Here we show that transglutaminase 2 (TG2), which is upregulated in HD, exacerbates transcriptional dysregulation by acting as a selective corepressor of nuclear genes. TG2 inhibition by RNA knockdown, genetic deletion, or administration of a novel irreversible, peptide-based TG2 inhibitor (ZDON) de-repressed

ORGANISM(S): Mus musculus

SUBMITTER: Giovanni Coppola 

PROVIDER: E-GEOD-21237 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress