Effects on Murine Behavior and Lifespan of Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h Knockdown

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Huntington’s disease (HD) is an inherited genetic disorder that leads to degeneration of brain cells and consequently to abnormal body movements, decreased mental capacity, and death. It is one of a group of untreatable degenerative neurological and neuromuscular diseases caused by expansion of gene segments containing multiple tandemly arrayed copies of short DNA sequences called trinucleotide repeats (TNRs). We report here that interference with production of a protein, SUPT4H, that is differentially needed for transcription through mutant Htt genes containing expanded TNRs reduces synthesis of abnormal Htt messenger RNA and protein, decreases HTT aggregates in murine brains, delays the occurrence of pathological features of HD, and prolongs HD mouse lifespan. Our results suggest that targeting of SUPT4H may be of value in the treatment of HD.

Vyšlo v časopise: Effects on Murine Behavior and Lifespan of Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h Knockdown. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005043
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005043

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