Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington's disease models.

ABSTRACT: Huntington's disease (HD) is a fatal neurodegenerative disease caused by a trinucleotide repeat expansion in exon 1 of the huntingtin gene (HTT) that results in toxic gain of function and cell death. Despite its monogenic cause, the pathogenesis of HD is highly complex, and increasing evidence indicates that, in addition to the full-length (FL) mutant HTT protein, the expanded exon 1 HTT (HTTexon1) protein that is translated from the HTT1a transcript generated by aberrant splicing is prone to aggregate and might contribute to HD pathology. This finding suggests that reducing the expression of HTT1a might achieve a greater therapeutic benefit than targeting only FL mutant HTT. Conversely, strategies that exclusively target FL HTT might not completely prevent the pathogenesis of HD. We have

SUBMITTER: Sogorb-Gonzalez M 

PROVIDER: S-EPMC11629698 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature