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Full-Text Articles in Physical Sciences and Mathematics
Exogenous Factors That Impact Huntingtin Aggregation, Adam Skeens
Exogenous Factors That Impact Huntingtin Aggregation, Adam Skeens
Graduate Theses, Dissertations, and Problem Reports
While expansion of a polyglutamine (polyQ) domain is the immediate cause of huntingtin (htt) aggregation associated with Huntington’s Disease (HD), other cellular factors modify aggregation. These include interactions with cellular membranes, protein biding partners, molecular crowding, and proteinaceous seeds. Here, two important factors are biophysically characterized: 1) the interaction of htt with endomembranes and 2) proteinaceous seeds obtained from a variety of htt-derived peptides. In the first project, the aggregation of htt at bilayer interfaces and in the presence of divalent cations was investigated. A major cellular factor implicated in altered htt aggregation is the binding of lipids. Furthermore, the …
Investigation Of Early Complex Formation Of Huntingtin Protein With And Without Lipids, Alyssa R. Stonebraker
Investigation Of Early Complex Formation Of Huntingtin Protein With And Without Lipids, Alyssa R. Stonebraker
Graduate Theses, Dissertations, and Problem Reports
Huntington’s disease (HD) is a fatal neurodegenerative disease caused by the expansion of the polyglutamine (polyQ) domain of the huntingtin protein (htt). The expansion of the polyQ domain beyond a threshold of approximately 35 repeats triggers complex toxic aggregation mechanisms and results in altered interactions between htt and lipid membranes. Many factors modulate these processes. One such modulator includes sequences flanking the polyQ domain, most notably the first 17 amino acids at the N-terminus of the protein (Nt17), and environmental factors including the presence of membranous structures. Nt17 has the propensity to form an amphipathic a-helix in the presence of …