Format

Send to

Choose Destination
See comment in PubMed Commons below
Protein Sci. 2009 Nov;18(11):2231-41. doi: 10.1002/pro.234.

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

Author information

1
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

Erratum in

  • Protein Sci. 2013 Nov;22(11):1688.

Abstract

Protein aggregation is a common feature of late onset neurodegenerative disorders, including Alzheimer's disease. In Alzheimer's disease, misassembly of the Abeta peptide is genetically linked to proteotoxicity associated with disease etiology. A reduction in Abeta proteotoxicity is accomplished, in part, by the previously reported Abeta 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 Abeta disaggregation kinetics accomplished by the exogenous application of C.elegans extracts. With this assay we demonstrate that the Abeta 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. Abeta 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.

PMID:
19701939
PMCID:
PMC2788278
DOI:
10.1002/pro.234
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center