Probing the aggregation landscape of Tau
In the tauopathy group of neurodegenerative diseases, the intrinsically disordered protein Tau undergoes a transition from its native disordered state into insoluble, pathological amyloid fibrils, such as those found in the neurofibrillary tangles of Alzheimer’s disease (AD). The mechanisms of Tau’s aggregation are still unclear, despite decades of research.
This talk will describe the driving forces of aggregation that arise from modifications to Tau’s primary sequence. Using electron paramagnetic resonance and electron microscopy, I will explore how aggregation is enhanced by lower conformational degrees of freedom in fragmented forms of Tau. Additionally, I will describe how a disruption to the protein hydration shell by the hereditary mutation P301L favors aggregation.