This work validates PIP4K gamma as pharmacological target to ameliorate Huntington's disease.

In a premanifest mouse model of Huntington's disease at a stage very far from disease onset, significant network and behavior dysregulation was found, being rebalanced by treatment with metformin.

Live imaging captures dynamics of Huntingtin aggregates plaguing the genome and waylaying target search.

Uninterrupted CAG repeat length determines onset age in Huntington's disease, and therefore, base editing strategies to generate CAA interruption offer new therapeutic opportunities as they diminish the disease-causing mutation.

Cross-species transcriptomic analysis and high-throughput behavioral assays in a Drosophila model of Huntington's disease show that downregulation of glial genes involved in synaptic function compensates for disease-related excitotoxicity.

A novel BAC226Q mouse recapitulating robust, age-dependent, progressive Huntington’s disease (HD)-like phenotypes will be a valuable tool for studying disease mechanisms, identifying biomarkers, and testing gene-targeting therapeutic approaches for HD.

Genetic knockout of Hdac2 modifies molecular and cellular phenotypes in Huntington’s disease mice and has a prominent transcriptional regulatory role in adult medium spiny neurons.

Cryo-electron tomography reveals how a chaperone protein called TRiC reduces the ability of pathogenic mutant huntingtin proteins to form aggregates.

Structural and biochemical analysis of full-length huntingtin protein illuminates the impact of the polyglutamine region on its structure and function.

The polyQ tract of pathogenic Huntingtin causes aggregation when expanded in Huntington’s disease, but its two flanking domains control its conformational landscape, proteostasis and neurotoxicity.