Modulating the ubiquitin-proteasome system in human diseases

The removal of misfolded or otherwise damaged proteins from the intracellular environment is of critical importance for cells.

The ubiquitin-proteasome system (UPS) is a central player in the cellular protein quality control as this is the primary proteolytic system responsible for the destruction of misfolded and dysfunctional proteins.

In recent years, both inhibition and stimulation of the UPS have gained credit as means for therapeutic intervention in human diseases.

On the one end, cancer cells typically produce high levels of misfolded proteins, which make them exquisitely sensitive to drugs that curtail UPS activity.

On the other hand, stimulation of the UPS may prevent accumulation of aggregation-prone proteins in neurons, which plays a central role in a variety of age-related, neurodegenerative disorders.

For almost two decades, our research has been dedicated to understanding the role of the UPS in cancer and neurodegenerative diseases.

As a logical continuation, we wish now to move our research to the next level by exploring new strategies for modulating the UPS in these diseases.

To this end, we will characterize potential therapeutic targets and compounds that we have identified in screens for modulators of UPS activity.

With the long-term objective to explore novel strategies for modulation of the UPS in clinically relevant settings, we anticipate that these studies we will identify new regulatory pathways amenable to therapeutic intervention.