The abstract is read at the publisher; the summary is JClub's.
A time-resolved proteomics study in a huntingtin-expressing in vitro cell model found a two-stage proteome response, with 85% of altered proteins reversing direction between 72 h and 144 h.
- Why it matters: The temporal order of pathogenic changes in Huntington disease is unclear, limiting how therapies can be timed to target early versus late mechanisms.
- What they did: Cells expressing polyglutamine-expanded huntingtin were profiled at 72 h and 144 h, revealing two distinct proteomic stages and a genotype-by-time interaction; an AI-assisted, direction-aware drug repurposing screen then used 1,712 differentially abundant proteins.
- The result: Early changes enriched RNA-processing, splicing, and protein-synthesis proteins, while late changes depleted many of these and instead dominated mitochondrial energy-metabolism; respiratory-chain subunits shifted from reduced at 72 h to broadly increased at 144 h, and 56 druggable targets mapped to agents with current regulatory approval.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.