Multiscale simulations reveal the driving forces underlying V337M-induced Tau core fragment aggregation

Key Points

• The aim is to understand how the V337M mutation influences Tau aggregation, a key factor in tauopathies.
• Multiscale simulations were conducted to analyze the structural changes in Tau due to the V337M mutation.
• Focus was on the aggregation-prone PHF6** motif of Tau.
• Interactions between Tau fragments were assessed to reveal driving forces of aggregation.
• Simulations showed significant alterations in the aggregation pathway due to the V337M mutation.
• Increased probability of Tau core fragment aggregation was observed compared to wild-type Tau.
• Key driving forces identified include structural changes induced by the mutation, affecting Tau dynamics.