Biochemistry, Biophysics, and Structural Biology Commons^™

Targeting The Nt17 Of The Huntingtin Protein Via Natural And Chemical Modifications: Impact On Aggregation And Membrane Interactions, Faezeh Sedighi

Graduate Theses, Dissertations, and Problem Reports

Huntington Disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine domain (polyQ) in the first exon of the huntingtin protein (htt-exon1). The major hallmark of HD is the accumulation of aggregates into proteinaceous inclusion bodies. PolyQ expansion in huntingtin promotes self-assembly into a variety of toxic aggregates such as oligomers, fibrils, and amorphous aggregates. The resulting heterogeneous mixture of distinct species makes it difficult to assign a toxic function to specific aggregate structures. In addition, htt interacts with a variety of membranous surfaces. The first 17 amino acids (Nt17) of htt directly flanking the polyQ domain functions …