Polyglutamine Protein Aggregation: Molecular Structure and Pathogenic Mechanisms

This lecture by the instructor delves into the role of beta-hairpins in the nucleation and propagation of polyglutamine protein aggregation, focusing on Huntington's disease. The presentation covers the molecular structure of misfolded polyglutamine proteins, the impact of polyQ length on disease onset, and the formation of toxic fibrils. Through experiments and simulations, the lecture explores the complex pathways of polyQ aggregation, the structural features of HttEx1 fibrils, and the modulating effects of chaperones. The discussion extends to the oligomeric DNAJB8 structures, the nucleation process, and the potential therapeutic implications of inhibiting beta-hairpin formation.