Targeting early protein changes in devastating neurodegenerative diseases

Miguel Mompeán

Agencia Estatal Consejo Superior de Investigaciones Científicas, M.P., Spain

Amyotrophic lateral sclerosis and frontotemporal dementia are neurodegenerative diseases with limited treatment options. In both, certain proteins inside nerve cells lose their normal organisation and form abnormal solid deposits, but the early, potentially reversible events behind this change remain unknown. This project investigates why flexible protein assemblies gradually become rigid with the goal of blocking this process.

Experts in structural biology, biophysics and neurodegeneration will study how flexible assemblies transition to rigid states from their earliest stages, focusing on the role of cell membranes and interacting proteins in this process. The researchers will then test whether short molecules inspired by natural interactions can preserve flexibility and delay harmful aggregation.

By targeting early, potentially reversible events rather than only final deposits, the project could open new therapeutic avenues for amyotrophic lateral sclerosis and related disorders. The findings may also improve understanding of how neurodegeneration begins and support future treatments that target the mechanisms triggering harmful aggregation.

Membrane-Encoded Liquidity and Transitions of TDP-43 Assemblies

€500,000.00