Abstract

Nine different neurodegenerative disorders including Huntington’s disease are associated with polyglutamine expansions. In vivo, proteins with polyglutamine expansions are unstable and are processed by proteolysis. Fragments of proteolysis are rich in aggregation-prone polyglutamine. Recent results suggest that the mechanisms by which polyglutamine-rich fragments aggregate are rather complex and these complexities derive from the role of polyglutamine length and sequence context. This talk will present some of these complexities that have been discovered using a series of biophysical studies including atomistic simulations, spectroscopy, and polymer physics theories. Implications for the role of polyglutamine aggregation in neurodegeneration will also be discussed.