UC Irvine

The proteasome is an essential enzyme complex in cells whose main responsibility is to degrade proteins. Proteins can be degraded through either a ubiquitin-dependent or -independent mechanism by the proteasome. A variety of small molecules have been discovered that can increase the rate of protein degradation through either mechanism. However, stimulation of the ubiquitin-independent system is likely to be the most therapeutically impactful for protein-accumulation diseases. Preliminary evidence has demonstrated efficacy of this approach for reducing proteins associated with disease. To advance the field forward, validation of this mechanism in a disease model as well as more detailed studies on how much stimulation is required to achieve a therapeutic effect must be performed.