Polyglutamine aggregation in Huntington and related diseases

Adv Exp Med Biol. 2012;769:125-40. doi: 10.1007/978-1-4614-5434-2_8.

Abstract

Polyglutamine (polyQ)-expansions in different proteins cause nine neurodegenerative diseases. While polyQ aggregation is a key pathological hallmark of these diseases, how aggregation relates to pathogenesis remains contentious. In this chapter, we review what is known about the aggregation process and how cells respond and interact with the polyQ-expanded proteins. We cover detailed biophysical and structural studies to uncover the intrinsic features of polyQ aggregates and concomitant effects in the cellular environment. We also examine the functional consequences ofpolyQ aggregation and how cells may attempt to intervene and guide the aggregation process.

Publication types

  • Review

MeSH terms

  • Cellular Microenvironment
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / physiopathology
  • Mutation
  • Peptides / chemistry*
  • Peptides / metabolism
  • Protein Binding
  • Protein Folding
  • Proteostasis Deficiencies / genetics
  • Proteostasis Deficiencies / metabolism*
  • Proteostasis Deficiencies / physiopathology

Substances

  • Peptides
  • polyglutamine