A kinetic assessment of the C. elegans amyloid disaggregation activity enables uncoupling of disassembly and proteolysis

Jan Bieschke, Ehud Cohen, Amber Murray, Andrew Dillin, Jeffery W. Kelly

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Protein aggregation is a common feature of late onset neurodegenerative disorders, including Alzheimer's disease. In Alzheimer's disease, misassembly of the Aβ peptide is genetically linked to proteotoxicity associated with disease etiology. A reduction in Aβ proteotoxicity is accomplished, in part, by the previously reported Aβ disaggregation and proteolysis activities-under partial control of heat shock factor 1, a transcription factor regulating proteostasis in the cytosol and negatively regulated by insulin growth factor signaling. Herein, we report an improved in vitro assay to quantify recombinant fibrillar Aβ disaggregation kinetics accomplished by the exogenous application of C. elegans extracts. With this assay we demonstrate that the Aβ disaggregation and proteolysis activities of C. elegans are separable. The disaggregation activity found in C. elegans preparations is more heat resistant than the proteolytic activity. Aβ disaggregation in the absence of proteolysis was found to be a reversible process. Future discovery of the molecular basis of the disaggregation and proteolysis activities offers the promise of delaying the age-onset proteotoxicity that leads to neurodegeneration in a spectrum of maladies. Published by Wiley-Blackwell.

Original languageAmerican English
Pages (from-to)2231-2241
Number of pages11
JournalProtein Science
Volume18
Issue number11
DOIs
StatePublished - Nov 2009

Keywords

  • Abeta
  • Alzheimer's disease
  • Disaggregation
  • Proteolysis

Fingerprint

Dive into the research topics of 'A kinetic assessment of the C. elegans amyloid disaggregation activity enables uncoupling of disassembly and proteolysis'. Together they form a unique fingerprint.

Cite this