Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures

ABSTRACT: Huntington's disease (HD) is a debilitating neurodegenerative disorder affecting an individual's cognitive and motor abilities. HD is caused by mutation in the huntingtin gene producing a toxic polyglutamine-expanded protein (mHTT) and leading to degeneration in the striatum and cortex. Yet, the molecular signatures that underlie tissue-specific vulnerabilities remain unclear. Here, we investigate this aspect by leveraging multi-epitope protein interaction assays, subcellular fractionation, thermal proteome profiling, and genetic modifier assays. Use of human cell, mouse, and fly models afforded capture of distinct subcellular pools of epitope-enriched and tissue-dependent interactions linked to dysregulated cellular pathways and disease relevance. We established an HTT association with ne

SUBMITTER: Joshua, L Justice 

PROVIDER: S-SCDT-10_1038-S44320-025-00096-3 | biostudies-other |

REPOSITORIES: biostudies-other