Poster #032
Characterizing proteasomal degradation of protein tau
Mentors: Dr. Bryan Ryder, PhD (Postdoc Mentor), Dr. Jason Gestwicki, PhD (PI)
Alzheimer’s disease is a neurodegenerative disease where one’s memory deteriorates with age. AD begins in the brain when protein tau aggregates and builds plaques that disrupt communication in the brain. Tau is degraded by the proteasome (20S) upon activation from a proteasome activator (PA) that opens the gated channel where the tau can enter the protease chamber. It is hypothesized that aggregation-prone tau is more difficult to degrade than wild-type tau. To test this, PA26 was used as a model proteasome activator, as it is known to promote tau degradation. A proteasome degradation assay with SDS-PAGE was used to compare degradation efficiency of different tau species, based on aggregation potential. Heat denaturation was used to improve degradation of more aggregation-prone tau species. By understanding the limitations of how the proteasome degrades tau, new therapeutics can be designed to assist the proteasome in degrading disease forms of tau.