Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways

Peter M. Douglas, Daniel W. Summers, Douglas M. Cyr

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

Abstract

The self-association of misfolded or damaged proteins into ordered amyloid-like aggregates characterizes numerous neurodegenerative disorders. Insoluble amyloid plaques are diagnostic of many disease states. Yet soluble, oligomeric intermediates in the aggregation pathway appear to represent the toxic culprit. Molecular chaperones regulate the fate of misfolded proteins and thereby influence their aggregation state. Chaperones conventionally antagonize aggregation of misfolded, disease proteins and assist in refolding or degradation pathways. Recent work suggests that chaperones may also suppress neurotoxicity by converting toxic, soluble oligomers into benign aggregates. Chaperones can therefore suppress or promote aggregation of disease proteins to ameliorate the proteotoxic accumulation of soluble, assembly intermediates.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalPrion
Volume3
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Amyloid
  • Chaperone
  • Heat shock protein
  • Hsp40
  • Hsp70
  • Prion
  • Protein aggregation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Infectious Diseases

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