Hunting-ton for new proteases: MMPs as the new target?

Mutant huntingtin proteolysis mediated by various proteases plays a key role in Huntington's disease (HD) pathogenesis. In this issue of Neuron, Miller et al. have identified 11 proteases, including matrix metalloproteinases (MMPs), that when inhibited reduce huntingtin proteolysis and produce beneficial therapeutic effects. These findings provide new insights into huntingtin proteolysis and its potential as a therapeutic target.