Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilization

Michelle A. Poirier, Huilin Li, Jed Macosko, Shuowei Cai, Mario Amzel, Christopher A. Ross

Research output: Contribution to journalArticle

Abstract

The pathology of Huntington's disease is characterized by neuronal degeneration and inclusions containing N-terminal fragments of mutant huntingtin (htt). To study htt aggregation, we examined purified htt fragments in vitro, finding globular and protofibrillar intermediates participating in the genesis of mature fibrils. These intermediates were high in β-structure. Furthermore, Congo Red, a dye that stains amyloid fibrils, prevented the assembly of mutant htt into mature fibrils, but not the formation of protofibrils. Other proteins capable of forming ordered aggregates, such as amyloid β and α-synuclein, form similar intermediates, suggesting that the mechanisms of mutant htt aggregation and possibly htt toxicity may overlap with other neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)41032-41037
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number43
DOIs
StatePublished - Oct 25 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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