HCR.20.054 – Keeping proteins liquid to prevent ALS

Route: Health care research, sickness prevention and treatment

Cluster question: 082 How does the central nervous system develop and how can we counteract degeneration processes in that system?

Patients with Amyotrophic lateral sclerosis (ALS) become unable to use their muscles because the brain is no longer able to send the required signals. In the Netherlands, 500 people are diagnosed with this and similar diseases every year, but no drug or treatment is currently known. Very recently, a new idea has emerged: some proteins in our brain cells need to stay in a special ‘liquid’ state, and hence forming droplets within cells. Once this is not possible anymore these proteins form solid structures, like water freezing into ice. This transition from liquid to solid could represent the point of no return for ALS development, but also for many other diseases were these solid structures can be observed, like Parkinson’s disease and Alzheimer’s Disease. This novel way of thinking about proteins suggests that ALS might be prevented by preserving this liquid state. We plan to rebuild these droplet-like structures in the lab in a setting where we can control all parameters, and use special tools to add and remove single proteins to get a better understanding about the forces and processes that are involved in these processes. We will use this to develop theoretical models of these phases that can be simulated in a computer, but also as a starting point to then transfer the knowledge generated in this system to biological systems of increasing complexity and finally to patients at the risk of developing ALS. All of this will guide us in the development of treatments that keep these proteins liquid or even de-freeze them after they have solidified. For water this can be simply achieved by adding salt, however for proteins were the solidification is often irreversible, like the boiling of an egg, we expect that this process is more complex.

Keywords

ALS, Protein aggregation, protein phase separation

Other organisations

UMCG

Submitter

Organisation AMOLF
Name Prof. Dr. Ir. Sander J. Tans
E-mail tans@amolf.nl
Website https://amolf.nl/people/sander-tans