Defining the Htt-exon1 aggregation state induced transcriptomic changes in Huntington's disease

Abstract

Huntington's disease (HD) is a trinucleotide repeat expansion disorder that is caused due to a defect in the exon 1 of the Huntingtin gene. The defect is in the number of polyglutamine coding CAG repeats. If the number of glutamine repeats in the huntingtin protein (Htt) exceeds 35 the soluble Htt protein becomes sticky, aggregate prone and clumps together to form micro-meter sized inclusions, which is the key feature in HD. There is mounting evidence that the soluble form of mutant Htt is highly proteotoxic to cells and increases the risk of cell death prior to aggregation, whereas aggregates impart distinct changes to cellular health, potentially adapting the cell to stressors and negating..