Figure 1.

Schematic model summarizing findings. In HD, translation of the trinucleotide repeat expansion that exceeds 40 repeats in the HD gene leads to expression of mutant HTT (mHTT), which leads to the symptoms and neuropathology associated with the disease. The expanded polyglutamine also causes mHTT to misfold, and the resulting aggregates can worsen symptoms. These aggregated structures are handled by WDFY3-mediated selective macroautophagy in the adult brain, and decreasing WDFY3 levels will augment aggregation, and drive pathology.