Oxidation Promotes Distinct Huntingtin Aggregates in the Presence and Absence of Membranes.

ABSTRACT: Expansion of a polyglutamine (polyQ) domain within the first exon of the huntingtin (htt) protein is the underlying cause of Huntington's disease, a genetic neurodegenerative disorder. PolyQ expansion triggers htt aggregation into oligomers, fibrils, and inclusions. The 17 N-terminal amino acids (Nt17) of htt-exon1, which directly precede the polyQ domain enhances polyQ fibrillization and functions as a lipid-binding domain. A variety of post-translational modifications occur within Nt17, including oxidation of two methionine residues. Here, the impact of oxidation within Nt17 on htt aggregation both in the presence and absence of lipid membranes was investigated. Treatment with hydrogen peroxide (H₂O₂) reduced fibril formation in a dose-dependent manner, resulting in

SUBMITTER: Adegbuyiro A 

PROVIDER: S-EPMC9296575 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature