Protein quality control in health and disease

Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and prion disease are devastating and affect an increasing number of people in ageing populations. Each disease is caused by the progressive dysfunction and death of specific nerve cells in selective regions of the brain due to the accumulation of proteins of aberrant shape. We have identified selective, safe and potent small molecule inhibitors that enhance the natural defence systems against misshapen proteins and in mice, the inhibitor protects against Huntington’s disease.

In this work, we will examine the benefit of our inhibitors in models of common neurodegenerative diseases, characterise their mode of action in vitro and in cells and search for other targets that could be inhibited to enhance different cellular defence mechanisms. We will target phosphatases, a class of enzymes that were thought to be undruggable. We will manipulate fundamental cellular processes to correct the cellular dysfunction at the origin of diverse diseases.

The knowledge and the inhibitors from our work may be used to develop treatments for a group of devastating diseases.