Membranes as targets and modifiers of mutant huntingtin aggregation.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene, resulting in an expanded polyglutamine (polyQ) tract in HTT protein. Expanded polyQ tracts cause mutant HTT (mHTT) to aggregate and accumulate as cellular inclusions. Recent studies highlight the interactions between mHTT and different cellular membranes that contribute to HD pathogenesis. Beyond being targets for mHTT-induced damage, membranes modify mHTT aggregation in a complex manner. This review explores the membrane abnormalities observed in a variety of HD models and the interplay between binding to and subsequent aggregation of mHTT on membranes, with an emphasis on N-terminal mHTT fragments. Understanding mHTT-lipid interactions may provide potential targets for therapeutic intervention that would complement other efforts.